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135 Cards in this Set
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• In what way can the shape of the nucleus change?
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o Depending on the state of the cell, the nucleus can change its shape/length o Depending on its metabolic activity the nucleus can become folded/invaginated |
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• What are the 2 types of chromatin? How does the ratio of these 2 types differ w/ different cells? |
o There is hetero and eu chromatin. Hetero is more condensed w/ shorter linker regions. Eu is less condensed and there are longer spaces b/w the histones allowing for transcription. o Cells that are more metabolically active will have more euchromatin than hetero |
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• What is margination of the nucleus? When does it occur? |
o This is when the chromatin/genetic material are condensed and pooled along the membrane of the nucleus. This often indicates irreversible injury/necrosis. |
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• Describe the structures found in the nuclear matrix. Is there a lot of nothingness? |
o There is the nucleolus which contains ribobiogenesis functions. Chromatin is present holding the genetic material. There are nuclear pores all over. There are fiber like and granule like proteins throughout the matrix. Nuclear lamin is present too. |
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• How are vesicles and tubules found in the nucleus during viral infections like fibrotic lung disorder? |
o When the nucleus invaginates to increase the surface area, there are vesicles and tubules formed. This can build up and cause problems. o In fibrotic lung disorder, lung epi cells start to die and the other cells to compensate for this by proliferating and result in an accumulation of these vesicles and tubules |
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• What kind of inclusions can you find in the nucleus? |
o glycogen inclusions (w/ hepatitis, DM, or glycogen storage diseases) o lipid inclusions (in cells with lots of lipid interactions) o crystalline inclusions (oversaturation of proteins in viral infections like herpes and measles). o Lead inclusions |
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• What kind of vesicles will you see in the nucleus with the herpes virus? With the measles virus? |
o Herpes- circular vesicles o Measles- tube like vesicles |
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• What is the nucleolus? What kind of genetic material is found here? What compartments make up the nucleolus? What functions does the nucleolus have? What’s a specific protein we’d find here |
o Nucleolus is a subnuclear structure. o It has an FC, a DFC, and a GC. o Contains DNA and RNA (specifically 45S rRNA) for ribosome biogenesis. It also controls things like cell cycle, mitosis, cell growth, etc. o Specific protein you’d find here is nucleolin |
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• How does ribosome biogenesis occur? |
o The FC has the transcribed 45S rRNA, and it undergoes processing all throughout the nucleolus to eventually get 40S and 60S ribosome subunit that moves out of the nucleolus to the cytoplasm |
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• What does the size of the nucleolus depend on? How can it change? |
o The size and structure of the nucleolus directly relates to the number of ribosomes the cell needs to be made. More ribosomes mean bigger nucleolus. o You can also have multiple nucleoli in the cell. |
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• What does nucleolar enlargement mean? What causes it? What happens to the nucleolus? |
o This occurs when there is some stress to the nucleolus. o Stress could be related to cardio hypertrophy, MI, other CV problems o The nucleolus expands, it becomes more fibrillar and less granular, and there is increase in ribosome biogenesis |
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• What does nucleolar disruption mean? What causes it? What happens to the nucleolus? |
o This occurs when there is some stress to the nucleolus. o Stress could mean DNA damage, genotoxic stress, Actinomyocin D o You’ll see membrane disruption, separation of FC from GC, fragmentation, shrinking of nucleolus, unraveling of DNA, inhibition of transcription |
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• What does nucleolar margination indicate? Is it always pathogenic? |
o Nucleolar margination means that there is increased ribosomal biogenesis. Not always pathogenic BUT could be found in cancer cells as well. |
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• What is nucleolar regression? When can it happen? |
o This is when the nucleolus shrinks DUE to decreased ribosomal biogenesis. o This happens in cells that are older, or after irradiation, or RNA synthesis inhibition. |
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• How does cancer affect the nucleolus? |
o Cancer involves highly proliferating cells. So there is a huge increase in ribosome biogenesis. Could be shown to have larger nucleoli |
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• How do viruses like HIV with its REV protein affect the nucleolus? |
o There is indication that Viruses use the nucleoli in their infective process. HIV uses the REV protein to infect the nucleolus and mess with/disorganize the nucleolar proteins. This leads to nucleolar damage. |
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• How do neurodegenerative diseases like Alzheimer’s disease affect the nucleolus? |
o There is a link showing the decrease in the nucleolar functions w/ these diseases. There is less ribosome biogenesis b/c there is less metabolic activity. There could also be proteins that become faulty in these diseases |
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• What is the function of the mito? What shapes will you see the mito in? |
o Function is to provide energy to the cell by oxidative phosphorylation (making ATP) o Other jobs include heme/nucleotide/steroidhormone synthesis, Apoptosis, FA synthesis and oxidation. o You’ll see rod like shapes, circular shapes, or vesicular shapes depending on cell and cell function. |
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• What is the structure of the mito? What are some of the jobs the sections have? |
o Outer membrane which has pores to let proteins in and lipid metab proteins o Intermembrane space o Inner membrane is made up of the cristae and have the role of ETC o Matrix has dense granules and mito DNA and also involved in CAC. |
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• How many mito can be in a cell? What does that depend on? How many cristae are found in a mito and what does that depend on? What does zig zag or concentric cristae mean |
o There can be 100s of mito depending on the metabolic activity of the cell. More metabolic activity means more mito o There can be lots of cristae and this also depends on the metabolic activity of the cell. o Zig zag and concentric cristae are usually present in cells that are more metabolically active. |
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• What does a swollen mito indicate? |
o It shows that something is wrong b/c the function will be impaired. This means that ions as well as fluid are flowing into the mito and pushing aside the cristae. Could be from anything like starvation, HSV, yellow fever, etc. |
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• What does a giant mito indicate? |
o This can mean that the mito is getting bigger, or that mito are fusing together. Can happen with alcoholism, and vitamin/nutritional deficiencies |
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• What is mito hyperplasia indicative of? |
o This means that there is an increase in the number of mito. This happens if cells need more energy. found in areas like brown tissue, the heart, uterus, skeletal muscle, etc. |
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• What kind of inclusions can be found in the mito? |
o Glycogen o Lipids, if the mito can’t break it down or if the cristae are malfunctioning o Crystalline, if there is protein saturation. Can be due to viral infection like hepatitis, or alcoholism o Iron inclusions |
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• Where do the proteins found in the mito generally come from?
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o 95% of the proteins found in the mito are from the nucleus made in the cytoplasm and sent over to the mito. o There are only 13 proteins that are made by the mito and they’re all involved in the ETC |
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• Describe the process of the mito protein import from the nucleus. What is required of the signal sequence? |
o Proteins made in the cytoplasm have to have a mito targeting signal. The signal has to be basic and it forms an aliphatic alpha helix. o The proteins need to be unfolded and are bound by heat shock proteins (with the help of ATP) to be kept unfolded. o The signal seq binds to an import receptor that is near a translocator, TOM. The protein moves through TIM into the matrix and is bound to more heat shock proteins (w/ ATP help). Once the protein is imported it folds into the correct conformation. o There needs to be a negative matrix potential to allow the proteins to enter the mito |
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• How is the mito DNA organized? Where are all the protein coding regions found? What do they code for? |
o The mito DNA is small and circular. It has 2 chains, a heavy (outside) and light (inside). o All but one of the protein are coded by the heavy strand. And all the proteins made by the mito are used in the ETC. o There are no introns |
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• What are uncoupling proteins? |
o These are proteins that separate the ATP generation from the ETC. The concentration gradient is restored by allowing the H+ to pass back into the matrix with the help of these proteins. o They generate heat and are found in brown adipose tissues. |
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• How many ATPs are produced through the process of oxidative phosphorylation? |
o Anywhere from 30-36 (around 32) |
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• What role does the carnitine shuttle play in FA oxidation? How is this shuttle limited? |
o FAs are brought into the mito through diffusion or albumin. The carnitine shuttle is used to transport the long chain FAs. o CPT1 replaces the acetyl coa from the FA in the MOM with carnitine allowing it to flow into the MIM. Here CPT2 allows the replacement of the acetyl coa and recycles the carnitine back to the MOM. o Malonyl CoA inhibits the CPT1 and therefore CTP1 is the rate limiting step |
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• How does FA oxidation occur in mito? |
o Once the FAs are inside the mito matrix, the processing begins. 2 C chains are removed for every turn producing 1 FADH2, 1 NADH, and 1 Acetyl CoA. o These products can all be used in the CAC or the ETC to produce energy. |
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• In what situations is FA oxidation the primary source of energy? |
o Diabetic pts who have low glucose metabolism o in the heart for cardiac contractility o during starvation/caloric restriction o excessive exertion |
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• How is the Mito DNA different from the typical Mendelian inheritance? |
o Mito DNA is strictly inherited from the mother o Heteroplasmy- a mito can have multiple different mito genome due to mutations o Random segregation- the different mito genomes can split up during fission or replication. They can split up differently (5 normal 5 mutated, 6 normal 4 mutated, etc) o Threshold effect- b/c of the random segregation, there might not be a phenotypic mutation present even though there is a mutated genome. |
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• What role does the mito have in ROS ? |
o Complex 1 and 3 in the ETC leak out electrons occasionally which can combine w/ oxygen to make ROS. This can cause damage. The mito has SOD and catalase to convert ROS into H2O2 and then water/oxygen. o Double agent theory of ROS |
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• How can mutations in the mito affect the mito genome? What kinds of diseases doe we see? |
o There isn’t a lot of proofreading machinery in the mito genome so mutations can cause lots of damage. o MERFF (myoclonic epilepsy assoc w/ ragged red fibers) affects muscles o MELAS (mito encephalopathies w/ lactic acid and stroke like episodes) affects brain o LHON ( leber hereditary optic neuropathy) affects neurons in eye |
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• How does Mito DNA replication occur? What is needed? |
o Replication occurs at the point of origin on the heavy strand which is at the non-coding region. The replication begins on the heavy strand going in one direction until it meets the promoter of the light strand which goes in the other direction at which point it starts replicating the heavy strand. o We need an RNA polymerase and 2 transcription factors to lay down a primer. o We need a DNA polymerase (POLG) to bind to the primer o We need helper proteins like Twinkle to act as a helicase and mtSSB to hold the single strand together. |
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• How can mito mutations lead to aging? |
o There can be mutations that go unchecked leading to more and more mistakes that can cause more ROS leakages. This can ultimately lead to the aging of the individual. |
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• What role does mito play in IVF? What are the 2 procedures |
o There’s an autologous procedure called AUGMENT that takes the mito from immature oocytes and implants them in the mature oocytes for more energy/if the mother’s mitos weren’t functioning properly . o There’s a non-autologous procedure that uses a donor’s egg with their mito. It works by removing the donor’s nucleus and adding the mother’s nucleus to the donor egg and fertilizing it. |
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• Describe the morphological characteristics of a peroxisome. In what ways is it different from a mito? And how do human peroxisomes differ from mice ones?
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o Peroxisomes are single membraned respiratory organelles. o They don’t have 2 membranes, any DNA, or ATP generating abilities o Human perox don’t have a crystallized chore as mice do (b/c of urate oxidase) |
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• What are the 2 main enzymes that peroxisomes have? What are they used for? |
o The 2 main ones are oxidase and catalase. o The oxidase removes H from molecules and adds it to Oxygen making H2O2. o The catalase then uses the H2O2 for oxidative reactions (phenols, formic acid, and alcohol detox) resulting in water and oxygen which can be used for oxidative processes still. |
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• What functions does the peroxisome have? |
o Respiration o Detoxification o Gluconeogenesis o Major part of lipid metabolism o Intracellular signaling o Plasmologen synthesis o Cholesterol and bile acid synthesis. |
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• In what types of cells are perox more likely to be found? |
o Liver and kidney cells |
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• How do viruses like HIV and Rotavirus use perox? |
o They need perox to survive and maintain themselves .HIV needs perox in order to develop into AIDS. |
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• What are the theories behind how perox form? |
o One theory is that perox enz are made in the ER lumen and they gather altogether. ER then buds off with these proteins and forms a mature perox. o Another theory is that perox have proteins imported into them and then they divide/fissure. o Another theory is that mito membranes bud off containing proteins and lipids and then fuse with the pre-perox and form a mature perox. |
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• How are perox proteins imported into the perox? |
o Perox proteins have to have a targeting signals (either PTS1 or PTS2 but mostly 1) o These proteins w/ the signals bind to signal recognizing receptors called peroxins in the cytoplasm. o This complex then docks onto the perox and a transient pore allows the import of the proteins. o The PTS signals are then recycled o PEX genes code for the peroxins. |
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• What kind of perox damage results in Zellweger syndrome? Why does this happen? What kind of clinical characteristics are noticed? What cells are most often targeted? |
o Zellweger syndrome is caused by a general lack of perox function. This happens because there is a defect in the PEX gene that codes for the PTS1 and 2 signals. If there are PTS signals then perox proteins can’t get into the cell and it stops functioning. o This leads to lipid accumulation in cells. o Clinical characteristics are neurodegeneration, hepatic dysfunction and skeletal abnormalities. o Particularly hepatic and renal cells are targeted. |
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• How is the severity of the Zellweger syndrome determined? |
o The more catalase positive perox that lose their function, the more severe the condition. |
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• What are the 2 types of Adrenoleukodystrophy? |
o X-linked ALD and Neonatal onset ALD |
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• How does X-linked ALD develop? What is faulty in these indiv? What are the clinical characteristics? |
o There is a mutation in the ABCD1 gene that codes for a membrane transporter. This results in the inability to move in Long chain FAs to be metabolized, and therefore, accumulation in the cell. The white matter and the adrenal cortex will be destroyed. o Clinical characteristics is usually peripheral neuropathy |
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• How does neonatal ALD develop? What is faulty in these individuals? What are clinical characteristics? |
o There is a decrease in the number and size of perox present. Catalase activity is diminished. FA metabolism is decreased. o Clinical characteristics include seizures and myotonia |
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• Describe the morphology and general characteristics of the ER? |
o It is a single membraned organelle o It has netlike meshwork that extends throughout the cytoplasm. o SER and RER (SER has no cisternae while RER does) o Can change shape and function based on the cell. o Interacts with the MTs MFs |
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• Describe the protein transport to the RER |
o mRNA is bound by the ribosomes. There is some translation enough for a signal sequence to be visible. o The signal sequence binds to an SRP and that complex binds to the SRP receptor on the ER. o There is cotranslational translocation of the protein into the lumen of the ER. o Glycosylation occurs (adding N-linked oligosaccharides) and the protein is folded. o Protein is then sent to Golgi |
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• What happens if the protein isn’t folded properly? |
o It is digested by proteasome |
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• What are the functions of the RER? |
o It makes the proteins that are transported to the Golgi o It is involved in the glycosylation of proteins o Lipid synthesis. o Makes transmembrane proteins and proteins that are excreted |
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• What are the functions of the SER? |
o Involved in the synthesis of steroid hormones o Synthesis of cholesterol and glycoproteins o Removes Ca from muscle cells (sarcoplasmic reticulum) o Lipid transport |
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• What effects result in dilation and vesiculation of the RER? |
o This is when the RER swells and makes more vesicles. There is also degranulation. o This happens under chronic alcoholism or under protein synthesis arrest. |
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• What is cloudy swelling? |
o It is similar to the dilation and vesiculation of RER except that the mito is involved as well. o This can happen with starvation, hepatitis, scurvy, lack of O2 noxious influences |
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• What kind of inclusions occur in RER? |
o Proteins forming crystalline structures (rheumatoid arthritis) o Lipids o Viruses |
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• How does hypertrophy or atrophy of the RER and SER occur? How does this lead to tolerance? |
o If there is increased metabolic activity, then we’ll have a hypertrophy of the RER like in pregnancy o Inactive phagocytes becoming active can also cause this o SER hypertrophy occurs when there is a need for detox and drug clearance, making Cytp450. o Tolerance can occur b/c hypertrophy already occurred and there will a need for more drugs/alcohol for the same cytp450 effects after the initial ones. o Atrophy occurs if there is decreased protein synthesis |
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• What is Hereditary Spastic paraplegias caused by? What are the clinical characteristics of this? |
o This is a class of neuro disorders caused by ER morphologies that result from mutations. o This causes degeneration of the motor neurons in the corticospinal tract. o Clinical characteristics are limb spasticity, weaknesses in the limbs, and paralysis. |
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• What is the ER’s role in viral infections like Hep C, and Dengue virus? |
o The ER is thought to support the viral entry, assembly, and replication through its membranes |
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• How do proteins get to the Golgi?
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o Vesicles that bud from the ER and are coated with COP2 proteins. They interact together to form vesicular tubular structures. These structures then move along MT with the help of motor proteins towards the Golgi complex. |
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• What is the golgi made of? How many are there? Where are they located? |
o It is a bunch of flattened sac like cisternae that are linked together. o They usually form 6 sacs to a golgi but can increase. There can also more complexes per cell. o They are usually found near the nucleus but they can move around (like in intestinal brush border) |
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• What roles do MTs play in the golgi? |
o They are VERY important to stabilize the Golgi o They are also important to move the vesicular clusters towards the golgi |
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• What functions do the Golgi have? |
o They are involved in protein packaging and movement to where they need to go o They are involved in post translational modifications o Essential to getting lysosomal proteins to lysosome. o Needed for membrane replenishment |
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• What are the theories of methods of transport in the Golgi? |
o One theory suggests that the vesicles bud off and move on to further cisternae. o Another theory suggests that proteins mature/process and move internally to the next cristae. |
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• What causes the hypertrophy of Golgi? |
o Increased protein production leads to hypertrophy. Increased number of Golgi complexes or cisternae |
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• What causes the atrophy of Golgi? |
o Toxic influences that cause an arrest of protein synthesis can lead to atrophy. Less proteins being made, less things need to be shuttled, and Golgi breakdown. |
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• What causes the fragmentation of the Golgi? |
o Neurodeg diseases like ALS or Alzheimer’s o Diseases like parkinson’s that have Gogli protein mutations o Polio virus that cause protein inhibition o Hep C o Human rhinovirus (common cold) |
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• What are lysosomes? What is their function? How do they do this? Why must they be kept intact? |
o Membrane bound organelles that serve as the cells digestive system. o They have a bunch of acid hydrolases that serve to break down particles and anything that comes inside the lysosomes. o They have to be kept intact b/c the pH of the lysosome is about 5.0 and the cell is 7.2 and the acid hydrolases will spill all over |
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• What are the different types of lysosomes? |
o Primary lysosomes which are made from the ER and packaged in the golgi o Secondary lysosomes which are a combo of primary lysosomes and a phagocytosed endosome (phagolysosome) o Autophagolysosome- a product of an autophagosome combining with a lysosome. |
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• What is lipofuscin and what is its significance in lysosomes? |
o Lysosomes are able to digest things but to a limited amount. In this case, the lysosomes can only digest so much lipids, and there can be an accumulation of lipids that aren’t digested that get darker and combine. This is lipofuscin. This can’t be digested and remains in lysosomes as residual bodies. |
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• How are lysosomes formed? |
o Lysosomal proteins are made in the ER and they are transported to the Golgi where they have to be processed. They NEED to have an M6P signal attached to them. And these signals allow them to bind to areas of the golgi with the M6P receptors. Once they’re bound, the vesicles bud off and form primary lysosomes |
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• Under what conditions will you see more autophagolysosomes? |
o This will happen under cases of cell stress where the cell is trying to survive so it eats up the parts that are damamged. More of these autophagosomes form to clear up the mess. o It can happen w/ UV, X-ray, viral infections, etc. |
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• How are lysosomes affected in cells that are aging (or lysosomes that are aging)? |
o They are slow for the autophagy process. o There is a decreased removal of unwanted products o More residual bodies form |
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• How do myelenoid bodies form? |
o This forms when there is are mutations/def in lysosomal proteins leading to lack of removal of lipids and glycogen. o Can be caused by viruses |
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• What are the biochemical and cellular basis of Lysosomal Storage diseases? |
o Mutations that cause as defective enz in lysosomes o Defective transport of lysosomal proteins from ER to lysosomes o Defective glycosylations of lysosomal proteins that either prevent proteins from getting to lysosomes or having decreased activity o Defective lysosomal membrane proteins |
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• What is Tay-Sachs disease caused by? What accumulates? What kind of clinical characteristics are seen? |
o It is an accumulation of gangliosides b/c of a beta-hexaminodase def. o This results in motor and mental deterioration and neuron destruction |
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• What is Neiman-Pick Disease caused by? What accumulates? What kind of clinical characteristics are seen? |
o Deficiency of sphingomyelinase leading to accumulation of sphingomyelin. o Characteristics- neuro degeneration and hepatosplenomegaly. You’ll see zebra bodies in the cells. |
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• What is Pompe’s disease? what accumulates? Clinical char? |
o Pompe’s disease is a deficiency alpha-glucosidase leading to accumulation of glycogen. o Can see skeletal and muscle weakness but it mainly targets the heart. |
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• What is Gaucher’s disease? what accumulates? Clinical Char? |
o Deficiency in glucocerebrosidase leads to accumulation of glucocerebrosides. o Clinical char- affects spleen , liver and bone marrow. |
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• What is I-Cell disease? what accumulates? Clinical char? |
o This is due to a problem in the M6P glycosylation. None of the lysosomal proteins get the M6P and can’t go to the lysosomes. Lysosome stops functioning and there is an accumulation of products in the lysosomes. |
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• How can Lysosomes be implicated in chronic inflammation like in rheumatoid arthritis? |
o Lysosomes play a role in inflamm. they can go to the site of damage and release the hydrolytic enz which might cause the inflamm. o In rheum arth. An accumulation of lysosomes release the enz into the synovial membranes |
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• How can asbestos and silicone affect lysosomes? |
o These particles are sharp and if inhaled can get into the lungh epi cells. Once they are taken up, they are brought to the lysosomes but they can’t be digested. And since they’re sharp they cut the membranes causing enz leakage. |
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• What is the structure of MTs?
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o They are hollow unbranched cylinders made from heterodimers of alpha and beta tubulin monomers. o the dimers bind with other dimers forming a protofilament o 13 protofilaments make 1 tubule w/ a lumen o They have a plus and minus end |
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• How are the MTs assembled and where does it occur? How are the monomers added/lost? What is treadmilling? |
o The alpha and beta monomers combine into dimers with the allosteric assoc of GTP. The apha subunit keeps the GTP while the beta subunit converts to GDP. o They form the protofilament. o Subunits can be added or removed from both ends but it is quicker on the plus side. o Treadmilling is when the dimers are recycled from the minus to the plus end, o The assembly occurs at MT organizing centers |
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• What are MT associated proteins and what do they do? where are they found? |
o MAP1 and MAP2 and tau. These are cross-linking proteins that are found mostly in neurons. |
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• What agent promotes MT assembly? How does it do this? How can this be used for cancer? |
o Taxol o It stimulates the polymerization of the MTs causing bundle formation o It prevents cell division and treadmiling so it can be used for cancer |
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• What agent causes disassembly of MT? how does it do this? |
o Colchicine causes disassembly. o It binds to the dimers and prevents them from being added on to the plus side. But the minus side isn’t affected. o The net effect is going to be a deterioration of the MTs. o This also inhibits cell division and MT funciton |
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• Where can MTs be found in the cell? |
o They can be found throughout the cytoplasm o Near the golgi moving the clusters o In cilia and flagella o Mitotic spindles |
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• What functions does the MT serve? |
o Development and maintenance of cell shape o Chromosome movements and mitotic spindle o Ciliary and flagellar movements o Intracellular movements o Organization of Golgi o Movement of motor proteins |
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• What does the structure of the cilia/flagella look like? |
o There are 9 pairs of MTs (A and B). o A is full B is partial but is closed by its assoc with A. o The pairs are arranged in a cylinder and have nexin proteins that connect them together. o There are dynein arms that connect from A to another pair’s B. and there are radial spokes that connect to the 2 pairs of MTs in the middle |
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• What are the 2 motor proteins used in the cell involving MTs and how do they work? |
o Kinesin which has 2 heavy chains that walk along the MT and a light chain that holds onto the vesicle. The Kinesin moves towards the plus end o Dynein which has 2 heavy chains that walk along the MT and a light chain that assoc with an intermediary protein that holds onto the vesicle. It moves towards the minus end. |
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• What is the structure of intermediate filaments? |
o These are long unbranched structures mostly made of actin and some myosin. |
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• How is actin assembled |
o It is made up of G-actin monomers that aggregate at a nucleus and form a helix shaped structure called F-actin filaments. o They have a plus and minus end and the plus end adds on monomers more quickly than the minus end. Treadmilling can occur here too |
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• What are the different types of Myosin? What are their structures and functions? |
o There are 3 major types. 1 2 and 5. o 1 and 5 have two heavy chain heads that bind to actin and a tail that binds to vesicles o 5 has one heavy chain head and is used in muscle contraction |
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• How are Actin cross linking proteins like alpha-actinin/filamin similar to fimbrin and fascin? How are they different? |
o These are both actin cross linking proteins o Filamin and alpha actinin are long cross linking proteins that connect actins in a 3D like network o Fascin and fimbrin are short cross linking proteins that connect them in bundles |
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• What agent is involved in MF disassembly? How does it do this? |
o Cytochalasin is involved in MF disassembly. It binds to the filaments and prevents any further additions onto the filament on the plus side. The minus side is not affected.o The net effect is a breakdown of actin |
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• What agent is involved in the MF stability? How does it do this? |
o Phalloidin is involved the stability. It binds to the filaments in a way that stabilizes it and prevents depolymerization. |
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• Where can MF be found in the cell? |
o They can be found in microvilli o Cytoplasm o Associated with the plasma membrane o In bundles of stress fibers o Part of muscles |
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• What functions do MF serve? |
o Cell division o Maintaining cell shape o Movement of material in cells o Movement of cells o Wound healing o Viral infectivity |
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• What are IFs and how are they assembled? |
o These are long unbranched structures that are fibrous proteins. o They have alpha helical structures. 2 monomers coil to form a dimer. 2 dimers form in a staggered tetramer. 2 tetramers form a staggered 8 membered rope like filament. o These are the strongest cytoskeletal structures. |
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• What are the different types of IFs in the cell? And where are they found? |
o Acidic keratins and Basic keratins both found in epithelial cells o A varied group found in glial cells muscle cells and neurons o Nervous system filaments found in neurons all over CNS o Lamins |
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• What is and does plectin Do? |
o Plectin is an IF associated protein that connects the IFs with MTs and MFs |
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• What functions does IFs serve? |
o They are fond in epidermal cells providing mechanical support o Interacting with MTs and MFs o In cell junctions o In sarcomeres o Wound healing |
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• What kind of abnormalities form from MT or MT associated proteins? What are clinical char? |
o Alzheimer’s disease from Tau hyperphosphorylation o Immotile cilia syndrome from deficiency in dynein. Leads to infertility, chronic sinusitis and URIs. o Charcot-Marie-Tooth Syndrome from MT motor protein defect KIFIB creating a roadblock. This leads to weakness and atrophy of limbs. |
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• What is the issue with the Tau protein in MTs that causes Alzheimer’s? and how can we stop this |
o There is a hyperphosphorylation in the Tau protein that leads to excessive neurotangles. The hyper phosphorylated tau proteins target unphosphorylated tau and block them from associating with the MTs leading to MT breakdown. o Therapies include a phosphatase that breaks up hyper phosphorylated tau. And inhibitors of the kinase that phosphorylates tau. |
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• How do viruses like Dengue and Flavivirus use actin? |
o They use it to enter through the cells and move about. They can also alter their processes and degrade/depolymerize them. |
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• What kind of abnormalities form from IF? What are clinical characteristics? |
o Epidermis bullosa simplex- disorder in keratin IFs can cause skin lesions and blisters o Emery-dreifuss muscular dystrophy- there is an AD version and Xlinked version both affecting the lamin and messing with the nuclear structure. o Hutchinson Gilford progeria syndrome (HGPS)- premature aging syndrome because of LMNA defect affecting the lamin gene o Epithelial cancers due to upregulation of plectin. This causes tumor progression |
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• What are the differences b/w integral and peripheral proteins?
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o Integral are incorporated into and pass through the lipid bilayer. o Peripheral proteins hang on either side of the membrane and often connect the integral proteins to the cell in some way |
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• What are the integral proteins found in the RBC membrane? What does each one do? |
o Band 3 is a multipass protein that has a glob domain in the cytosol. Its main role is for anion exchange and CO2 and O2 exchange o Glycophorin is a single pass protein with a glob on the EC space. Its major function is to maintain the negative charge of the RBC membrane. |
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• What are the major peripheral proteins and what do they do? |
o Alpha and beta spectrin which are filamentous proteins that have to bind together into a tetramer in order to function and maintain the cytoskeletal structure o Ankyrin which connects the spectrin to the band 3 protein o Band 4.1 which connects the spectrin to the glycophorin protein |
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• What is actin’s role in the RBC membrane? How is it connected? |
o Actin is a cytoskeletal protein and it is connected to band 4.1 and spectrin. It is the connection between the cytoskeletal proteins and the membrane |
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• In what shape does the actin filaments and spectrins bind together? |
o It binds together in a hexagonal like network of junctional complexes. |
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• What shape is the RBC normally? How sturdy/malleable is it? |
o They are usually bioconcave/disc like in shape. And the membrane is supposed to be very malleable so that it can withstand the microvasculature. |
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• What are some pathological changes that occur to RBC membranes? |
o Hereditary spherocytosis which is an AD disorder that results in the spherical shape of the RBCs. o Hereditary elliptocytosis which is an AD disorder that results in the elliptical shape of the RBCs o Hereditary pyropoikilocytosis which is a R disorder resulting in varied shape changes and thermos sensitivity. |
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• What is the cause of hereditary spherocytosis? What do the RBCs look like? What clinical characteristics are seen? |
o This is because of band 3 and Ankyrin deficiencies preventing sufficient binding to spectrin. This causes a spherical shape and a fragile RBC that gets trapped in microvasculature and has to be cleaned up by spleen. o Characterized by hemolytic anemia |
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• What is the cause of hereditary elliptocytosis? What do the RBCs look like? What clinical characteristics are seen? |
o The RBCs are elliptical in shape and are fragile as well. This is because of a deficiency in spectrin not being able to form tetramers. You’ll see more dimers than tetramers. o Characterized by hemolytic anemia |
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• What is the cause of hereditary pyropoikilocytosis? What do the RBCs look like? What clinical characteristics are seen? |
o The RBCs are varying in different shapes. This is because of a deficiency in spectrin not being able to form tetramers. You’ll see more dimers than tetramers and a decrease in actin binding to specrtin. Cells are unusually thermosensitive o Characterized by hemolytic anemia |
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• What are the different cell to cell junctions that are found ? |
o Tight junctions o Adherens o Desmosomes o Gap junctions |
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• How do tight junctions work? What is their role? What are the important proteins here? |
o Tight junctions work by connecting 2 cells in an occluding junction/tight seal to prevent leakage of any materials between them. There is no space between the cell. o Important proteins are claudin and occluding. |
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• How do adherens junctions work? What is their role? What are the important proteins here? |
o Adherens junctions are anchoring junctions that hold 2 cells together but have some EC space in between. o They are made with actin filaments bound to proteins on the IC side and a family of proteins called cadhedrins that dimerize and bind to the cadhedrins of the neighboring cell on the EC side. |
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• How do desmosomes work? What is their role? What are the important proteins here? |
o Desmosomes are anchoring junctions and are the strongest junction. They hold 2 cells together but have some space in between them. o They are made from IFs that are bound to a plaque on the IC side. Then there are a family of cadhedrins (like desmoglein) that dimerize and bind to the cadhedrins on the neighboring cell in the EC side. |
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• How do gap junctions work? What is their role? What are the important proteins here? |
o These are communicating junctions. There are pores on neighboring cells that have connexons on them. Each connexon is made from 6 connexins and they twist open and closed to allow fluids and particles to flow through between cells |
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• What are abnormalities from desmosomes? How can they be characterized (too many or little) |
o Too many desmosomes leads to Human warts, increased presence in problems like rheumatoid arthritis o Hailey hailey disease which is due to faulty connections b/w desmosomes. Happens when they aren’t matured enough and can lead to blisters. o Darier’s disease which is due to faulty IFs that can’t properly bind to the Desmosomes and results in blisters and epidermal separation. o Pemphigus vulgaris which is an auto immune disorder in which the cadhedrins specifically desmoglein is attacked by antibodies and taken up by the cell to be broken down by lysosomes. Leads to skin blisters and mucosal secretions |
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• What are changes or abnormalities from tight junctions? How can they be characterized? |
o In pregnancy, uterine wall epithelial cells form more tight junctions so that things don’t leak out. o Cholera toxin breaks down tight junctions in the intestinal cells causing diarrhea |
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• What are abnormalities in gap junctions? |
o There can be mutations in the connexins which cause problems for the connexon. in human inherited non syndromic deafness, the connexons are malfunctioning causing failure of potassium transfer in the hair cells of the ear/cochlea leading to deafness. |
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• When do we get more gap junctions forming? |
o During childbirth in the uterine smooth muscles o During insulin release in the pancreatic beta cells o Wound healing between the epithelial cells. |
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• How do abnormalities in adherens lead to metastasis of cancer? |
o So the cancer can’t spread unless it breaks through certain cells and gets to different areas. in some cases, the adherens junctions can break down leading to the metastasis of cancers |
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• What does the nuclear pore complex look like? |
o It is made up of over 30 proteins. There is a outer nuclear membrane and inner membrane, and transmembrane side of the protein. There are fibrils on both the cytosolic and nuclear side. The nuclear side fibrils form a basket for protein exchange. |
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• What is the function of the nuclear pore complex (aka porins)? How do they work? |
o They function to transport larger proteins in and out of the nucleus. Smaller proteins can just diffuse in and out of the nucleus but larger ones need help. o The proteins need a nuclear localization signal. They then need to bind to the signal receptor and the help of RAN GDP. These all combine and go into the matrix where RAN GTP dissociates the RAN GDP and protein from the signal receptor. Then the signal receptor and RanGTP get recycled out of the cell. Similar for protein export. |
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• How do the nuclear pore complexes vary? |
o They can vary in size and number. It depends on the metabolic activity of the cell |
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• How does the polio virus affect nuclear pores? How is this different from cardiovirus? |
o Poliovirus has a protease that messes with and destroys some of the proteins in the pore. This leads to increased bidirectional transport of any kinds of proteins. o It’s different from the cardiovirus b/c it actually destroys the pore proteins. |
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• How does the cardiovirus affect the nuclear pores? How is it different from the polio virus? |
o The cardiovirus alters the proteins in the nuclear pores but keeps the functional. This also allows for increased bidirectional permeability of proteins o It is different from the polio virus b/c it doesn’t break down the pore and its protiens |
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• What is triple A syndrome? What gene is mutated and protein is affected? What clinical char are noted? What systems are affected the most? |
o Triple A syndrome is due to a defect in the AAAS gene which codes for the Aladin protein. The Aladin protein which is in the cytoplasmic side, can’t bind to the necessary transmembrane protein in the nuclear pore complex. o This affects mostly the nervous system (CNS PNS and ANS). o Leads to inability to cry (ALacrima), swallow (Achalasia), aDrenal Insufficiency, Neurological abnormalities. |
