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76 Cards in this Set
- Front
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Saccharomyces cerevisiae
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• Yeast that have been used for years to make bread, wine, and beer
• Cells of this yeast identify their mates by chemical signaling • Cells of mating type "a" secrete a signaling molecule called "a" factor, which can bind to a specific receptor proteins on nearby "alpha" cells • At the same time, "alpha" cells secrete "alpha" factor, which binds to receptors on "a" cells • WIthout entering the cells, the two mating factors cause cells to grow toward each other and fuse, or mate, the two cells of opposite type • The new "a"/"alpha" cell contains all the genes of both original cells, a combination of genetic resources that provides advantages to the cell's descendants, which arise by subsequent cell divisions |
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signal transduction pathway
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• A series of steps linking a mechanical, chemical, or electrical stimulus to a specific cellular response
• Molecular details of these pathways in yeast and mammals are strikingly similar, suggesting that today's cell-signaling mechanisms evolved well before the first multicellular creatures appeared on Earth |
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quorom sensing
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• Bacterial cells secrete small molecules that can be detected by other bacterial cells
• The concentration of such signaling molecules, sensed by the bacteria, allows them to monitor the density of cells, known as this phenomenon • Allows bacterial populations to coordinate their behaviors so they can carry out activities that are only productive when performed by a given number of cells in synchrony |
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biofilm
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• A result of quorum sensing
• An aggregation of bacterial cells adhere to a surface; the cells generally derive nutrition from the surface they are on • Examples include the coating on a fallen log or leaves lying on a forest path, or on your teeth each morning |
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cell junctions
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• Found in both animals and plants, these serve to directly connect the cytoplasms of adjacent cells where they are present
• In these cases, signaling substances dissolved in the cytosol can pass freely between adjacent cells |
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cell-cell recognition
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• A process in which animal cells communicate via direct contact between membrane-bound cell-surface molecules
• Important in embryonic development and the immune response |
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local regulators
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A secreted molecule that influences cells near where it is secreted
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growth factors
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• A class of local regulators in animals, consists of compounds that stimulate nearby target cells to grow and divide
• Numerous cells can simultaneously receive and respond to the molecules produced by a single cell in their vicinity • This type of signaling is called paracrine signaling |
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paracrine signaling
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A form of cell-cell communication in which a cell produces a signal to induce changes in nearby cells, altering the behavior or differentiation of those cells
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synaptic signaling
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• Type of cell–cell communication that occurs across chemical synapses in the nervous system
• An electrical signal along a nerve cell triggers the secretion of neurotransmitter molecules carrying a chemical signal • There molecules diffuse across the synapse, the narrow space between the nerve cell and its target cell (other another nerve cell), triggering a response in the target cell |
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hormones
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• In multicellular organisms, one of many types of secreted chemicals that are formed in specialized cells, travel in body fluids, and act on specific target cells in other parts of the body, changing the target cells’ functioning
• Important in long-distance signaling |
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endocrine signaling
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• In animals, specialized cells release hormone molecules, which travel via the circulatory system to other parts of the body, where they reach target cells that can recognize and respond to the hormones
• Plant hormones (plant growth regulators) sometimes travel in vessels but more often reach their targets by moving through cells or by diffusing through the air as a gas |
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variation in hormones
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• The plant hormone ethylene is a gas that promotes fruit ripening and helps regulate growth, and is a hydrocarbon of only six atoms (C2H4), small enough to pass through cell walls
• The mammalian hormone insulin regulates sugar levels in the blood is a protein with thousands of atoms |
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transmission of signals through the nervous system
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• Can also be considered an example of long distance signaling
• An electrical signal travels the length of a nerve cell and is then converted back to a chemical signal when a signaling molecule is released and crosses the synapse to another nerve cell • Here it is converted back to an electrical signal • In this way, a nerve signal can travel along a series of nerve cells • Because some nerve cells are quite long, the nerve signal can quickly travel great distances |
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response of cells to secreted signal molecules
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• The ability of a cell to respond is determined by whether it has a specific receptor molecule that can bind to the signaling molecule
• The information conveyed by this binding, the signal, must then be changed into another form -- transduced -- inside the cell because the cell can respond |
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epinephrine
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• Also called adrenaline
• Stimulates the breakdown of the storage polysaccharide glycogen within liver cells and skeletal muscle cells • Glycogen breakdown releases the sugar glucose 1-phosphate, which the cell converts to glucose 6-phosphate • The cell (ex. a liver cell) can then use this compound, an early intermediate in glycolysis, for energy production • Alternatively, the compound can be stripped of phosphate and released from the liver cell into the blood as glucose, which can fuel cells throughout the body • Thus, one effect of this animal hormone is the mobilization of fuel reserves, which can be used by the animal to either defend itself (fight) or escape whatever elicited a scare (flight) |
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Sutherland's research & the stimulation of glycogen breakdown
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• Sutherland proposed that epinephrine stimulates glycogen breakdown by somehow activating a cytosolic enzyme
• Epinephrine could only activate glycogen phosphorylase when the hormone was added to a solution containing intact cells • Result was that epinephrine does not interact directly with the enzyme responsible for glycogen breakdown; an intermediate step or a series of steps must be occurring inside the cell • Also, the plasma membrane is somehow involved in transmitting the signal |
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overview of cell signaling
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• From the perspective of the cell
receiving the message, cell signaling can be divided into three stages: signal reception, signal transduction, and cellular response • When reception occurs at the plasma membrane, the transduction stage is usually a pathway of several steps, with each relay molecule in the pathway bringing about a change in the next molecule • The final molecule in the pathway triggers the cell’s response |
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reception
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• The target cell’s detection of a signaling molecule coming from outside the cell
• A chemical signal is “detected” when the signaling molecule binds to a receptor protein located at the cell’s surface or inside the cell |
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transduction
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• The binding of the signaling molecule changes the receptor protein in some way, initiating this process
• The transduction stage converts the signal to a form that can bring about a specific cellular response • Sometimes occurs in a single step but more often requires a sequence of changes in a series of different molecules -- a signal transduction pathway • The molecules in the pathway are often called relay molecules |
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response
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• In the third stage of cell signaling, the transduced
signal finally triggers a specific cellular response • The response may be almost any imaginable cellular activity -- such as catalysis by an enzyme (for example, glycogen phosphorylase), rearrangement of the cytoskeleton, or activation of specific genes in the nucleus • The cell-signaling process helps ensure that crucial activities like these occur in the right cells, at the right time, and in proper coordination with the activities of other cells of the organism |
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ligand
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• A molecule that binds specifically to another molecule, usually a larger one
• Binding generally causes a receptor protein to undergo a change in shape • For many receptors, this shape change directly activates the receptor, enabling it to interact with other cellular molecules • For other kinds of receptors, the immediate effect of ligand binding is to cause the aggregation of two or more receptor molecules, which leads to further molecular events inside the cell |
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cell-surface receptor molecules
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• Play crucial roles in the biological systems of animals, and their malfunctions are associated with many human diseases, including cancer, heart disease, and asthma
• They make up 30% of proteins, but they make up only 1% of proteins whose structures have been determined by X-ray chrystallography • Largest family consists of nearly 1,000 G protein-coupled receptors (GPCRs) |
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G protein-coupled receptor (GPCR)
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• Also called a G protein-linked receptor
• A signal receptor protein in the plasma membrane that responds to the binding of a signaling molecule by activating a G protein • A G protein-coupled receptor is a cell-surface transmembrane receptor that works with the help of a G protein, a protein that binds the energy-rich molecule GTP • Many different signaling molecules, including yeast mating factors, epinephrine and many other hormones, and neurotransmitters, use G protein-coupled receptors • These receptors vary in the binding sites for their signaling molecules (often referred to as their ligands) and also for different types of G proteins inside the cell • Nevertheless, G protein-coupled receptor proteins are all remarkably similar in structure • They make up a large family of eukaryotic receptor proteins with a secondary structure in which the single polypeptide, represented here as a ribbon, has seven transmembrane α helices, outlined with cylinders and depicted in a row for clarity • Specific loops between the helices form binding sites for signaling and G protein molecules • G protein-coupled receptor systems are extremely widespread and diverse in their functions, including roles in embryonic development and sensory reception • In humans, for example, vision, smell, and taste depend on such systems • Similarities in structure in G proteins and G protein-coupled receptors in diverse organisms suggest that G proteins and associated receptors evolved very early • G protein systems are involved in many human diseases, including bacterial infections • The bacteria that cause cholera, pertussis (whooping cough), and botulism, among others, make their victims ill by producing toxins that interfere with G protein function • Pharmacologists now realize that up to 60% of all medicines used today exert their effects by influencing G protein pathways |
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inactive G protein: step 1
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• Loosely attached to the cytoplasmic side of the membrane, the G protein functions as a molecular switch that is either on or off, depending on which of two guanine nucleotides is attached, GDP or GTP -- hence the term G protein
• When GDP is bound to the G protein, the G protein is inactive • The receptor and G protein work together with another protein, usually an enzyme |
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activation of G protein: step 2
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• When the appropriate signaling molecule binds to the extracellular side of the receptor, the receptor is activated and changes shape
• Its cytoplasmic side then binds an inactive G protein, causing a GTP to displace the GDP • This activates the G protein |
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triggering a cellular response: step 3
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• The activated G protein dissociates from the receptor, diffuses along the membrane, and then binds to an enzyme, altering the enzyme’s shape and activity
• Once activated, the enzyme can trigger the next step leading to a cellular response • Binding of signaling molecules is reversible: like other ligands, they bind and dissociate many times • The ligand concentration outside the cell determines how often a ligand is bound and causes signaling |
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hydrolization of GTP to GDP: step 4
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• The changes in the enzyme and G protein are only temporary because the G protein also functions as a GTPase enzyme -- in other words, it then hydrolyzes its bound GTP to GDP
• Now inactive again, the G protein leaves the enzyme, which returns to its original state • The G protein is now available for reuse • The GTPase function of the G protein allows the pathway to shut down rapidly when the signaling molecule is no longer present |
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receptor tyrosine kinases (RTK)
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• A receptor protein spanning the plasma membrane, the cytoplasmic (intracellular) part of which can catalyze the transfer of a phosphate group from ATP to a tyrosine on another protein
• Receptor tyrosine kinases often respond to the binding of a signaling molecule by dimerizing and then phosphorylating a tyrosine on the cytoplasmic portion of the other receptor in the dimer • The phosphorylated tyrosines on the receptors then activate other signal transduction proteins within the cell • RTKs belong to a major class of plasma membrane receptors characterized by having enzymatic activity • A kinase is an enzyme that catalyzes the transfer of phosphate groups • The part of the receptor protein extending into the cytoplasm functions as a tyrosine kinase, an enzyme that catalyzes the transfer of a phosphate group from ATP to the amino acid tyrosine on a substrate protein • Thus, receptor tyrosine kinases are membrane receptors that attach phosphates to tyrosines • One receptor tyrosine kinase complex may activate ten or more different transduction pathways and cellular responses • Often, more than one signal transduction pathway can be triggered at once, helping the cell regulate and coordinate many aspects of cell growth and cell reproduction • The ability of a single ligand-binding event to trigger so many pathways is a key difference between receptor tyrosine kinases and G protein-coupled receptors • Abnormal receptor tyrosine kinases that function even in the absence of signaling molecules are associated with many kinds of cancer |
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receptor tyrosine kinase binding: step 1
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• Many receptor tyrosine kinases have the structure depicted schematically
• Before the signaling molecule binds, the receptors exist as individual units referred to as monomers • Each has an extracellular ligand-binding site, an α helix spanning the membrane, and an intracellular tail containing multiple tyrosines |
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dimerization: step 2
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The binding of a signaling molecule (such as a growth factor) causes two receptor monomers to associate closely with each other, forming a complex known as a dimer (dimerization)
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activation of tyrosine kinase region: step 3
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• Dimerization activates the tyrosine kinase region of each monomer
• Each tyrosine kinase adds a phosphate from an ATP molecule to a tyrosine on the tail of the other monomer |
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cellular response: step 4
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• Now that the receptor is fully activated, it is recognized by specific relay proteins inside the cell • Each such protein binds to a specific
phosphorylated tyrosine, undergoing a resulting structural change that activates the bound protein • Each activated protein triggers a transduction pathway, leading to a cellular response |
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ligand-gated ion channel
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• A transmembrane protein containing a pore that opens or closes as it changes shape in response to a signaling molecule (ligand), allowing or blocking the flow of specific ions; also called an ionotropic receptor
• Contains a region that can act as a “gate” when the receptor changes shape • When a signaling molecule binds as a ligand to the receptor protein, the gate opens or closes, allowing or blocking the flow of specific ions, such as Na+ or Ca2+, through a channel in the receptor • Bind the ligand at a specific site on their extracellular sides |
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intial state of ligand-gated ion channel receptor: step 1
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A ligand-gated ion channel receptor gate remains closed until a ligand binds to the receptor
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binding of ligand to receptor: step 2
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• When the ligand binds to the receptor and the gate opens, specific ions can flow through the channel and rapidly change the concentration of that particular ion inside the cell
• This change may directly affect the activity of the cell in some way |
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closing of the gate: step 3
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• When the ligand dissociates from this receptor, the gate closes and ions no longer enter the cell
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ligand-gated ion channels in the nervous system
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• The neurotransmitter molecules released at a synapse between two nerve cells bind as ligands to ion channels on the receiving cell, causing the channels to open
• Ions flow in (or, in some cases, out), triggering an electrical signal that propagates down the length of the receiving cell • Some gated ion channels are controlled by electrical signals instead of ligands; these voltage-gated ion channels are also crucial to functioning of the nervous system |
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receptor tyrosine kinase function in cancer cells
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• Patients with breast cancel cells that have excessive levels of a receptor tyrosine kinase called HER2 have a poor prognosis
• Researchers have developed a protein called Herceptin that binds to HER2 on cells and inhibits their growth, thus thwarting further tumor development • In some studies, treatment with Herceptin improved patient survival rates by more than one-third |
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intracellular receptor proteins
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• Found in either the cytoplasm or nucleus of target cells
• To reach such a receptor, a chemical messenger passes through the target cell's plasma membrane • A number of important signaling molecules can do this because they are either hydrophobic enough or small enough to cross the hydrophobic interior of the membrane • Such hydrophobic chemical messengers include steroid hormones and thyroid hormones of animals • Another chemical signaling molecule with an intracellular receptor is nitric oxide (NO), a gas; its very small molecules readily pass between the membrane phospholipids |
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steroid hormones and intracellular receptors
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• In males, testosterone is secreted by cells of the testes
• It then travels through the blood and enters cells all over the body • However, only cells that contain receptor molecules for testosterone respond • In these cells, the hormone binds to the receptor protein, activating it • With the hormone attached, the active form of the receptor protein then enters the nucleus and turns on specific genes that control male sex characteristics |
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activated hormone-receptor complex's control of genes
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• Special proteins called transcription factors control which genes are turned on -- that is, which genes are transcribed into mRNA -- in a particular cell at a particular time
• The testosterone receptor, when activated, acts as a transcription factor that turns on specific genes • By acting as a transcription factor, the testosterone receptor itself carries out the complete transduction of the signal • Most other intracellular receptors function in the same way, although many of them, such as the thyroid hormone receptor, are already in the nucleus before the signaling molecule reaches them |
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a closer look at signal transduction pathways
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• The binding of a specific signaling molecule to a receptor in the plasma membrane triggers the first step in the chain of molecular interactions -- the signal transduction pathway -- that leads to a particular response within the cell
• The signal-activated receptor activates another molecule, which activates yet another molecule, and so on, until the protein that produces the final cellular response is activated • The molecules that relay a signal from receptor to response, relay molecules, are often proteins • It is important to remember that the original signaling molecule is not physically passed along a signaling pathway; in most cases, it never even enters the cell • Rather, at each step, the signal is transduced into a different form, commonly a shape change in a protein, which is often brought about by phosphorylation |
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protein phosphorylation and dephosphorylation
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A widespread cellular mechanism for regulating protein activity
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protein kinase
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An enzyme that transfers phosphate groups from ATP to a protein, thus phosphorylating the protein
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cytoplasmic protein kinases
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• Most act on proteins different from themselves
• Phosphorylate either of two other amino acids, serine or threonine • Such serine/threonine kinases are widely involved in signaling pathways in animals, plants, and fungi |
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phosphorylation cascade
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• Similar to many known pathways, including those triggered in yeast by mating factors and in animal cells by many growth factors
• Signal is transmitted by a cascade of protein phosphorylations, each bringing with it a shape change • Each such shape change results from the interaction of the newly added phosphate groups with charged or polar amino acids • Addition of phosphate groups often changes a protein from an inactive form to an active form • In other cases, phosphorylation may decrease the activity of the protein |
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protein phosphatase
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• An enzyme that removes phosphate groups from (dephosphorylates) proteins, often functioning to reverse the effect of a protein kinase
• By dephosphorylating and thus inactivating protein kinases, phosphatases provide the mechanism for turning off the signal transduction pathway when the initial signal is no longer present • Phosphatases also make the protein kinases available for reuse, enabling the cell to respond again to an extracellular signal • The phosphorylation-dephosphorylation system acts as a molecular switch in the cell, turning activities on and off, or up or down, as required • At any given moment, the activity of a protein regulated by phosphorylation depends on the balance in the cell between active kinase molecules and active phosphatase molecules |
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second messenger
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• A small, nonprotein, water-soluble molecule or ion, such as a calcium ion (Ca2+) or cyclic AMP, that relays a signal to a cell’s interior in response to a signaling molecule bound by a signal receptor protein
• This term is used because the pathway's "first messenger" is considered to be the extracellular signaling molecule -- the ligand -- that binds to the membrane receptor • Because it is small and water soluble, it can readily spread throughout the cell by diffusion (ex. cAMP carries signal initiated by epinephrine from the plasma membrane of a liver or muscle cell into cell's interior, where the signal eventually brings about glycogen breakdown) • Participate in pathways initiated by both G protein-coupled receptors and receptor tyrosine kinases |
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cyclic AMP (cyclic adenosine monophosphate)
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• A ring-shaped molecule made from ATP that is a common intracellular signaling molecule (second messenger) in eukaryotic cells; it is also a regulator of some bacterial operons
• Binding of epinephrine to the plasma membrane of a liver cell elevates the cytosolic concentration of this compound |
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adenylyl cyclase
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• An enzyme that converts ATP to cyclic AMP in response to an extracellular signal -- in one case, provided by epinephrine
• Epinephrine doesn't stimulate this enzyme directly • When epinephrine outside the cell binds to a specific receptor protein, the protein activates this enzyme, which in turn can catalyze the synthesis of many molecules of cAMP • In this way, the normal cellular concentration of cAMP can be boosted 20-fold in a matter of seconds • The cAMP broadcasts the signal to the cytoplasm |
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phosphdiesterase
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• An enzyme that breaks a phosphodiester bond in an oligonucleotide
• Converts cAMP to AMP |
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formation of cAMP
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• The second messenger cyclic AMP (cAMP) is made from ATP by adenylyl cyclase, an enzyme embedded in the plasma membrane
• Cyclic AMP is inactivated by phosphodiesterase, an enzyme that converts it to AMP |
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cAMP as a second messenger in a G protein signaling pathway
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• The first messenger activates a G protein-coupled
receptor, which activates a specific G protein • In turn, the G protein activates adenylyl cyclase, which catalyzes the conversion of ATP to cAMP • The cAMP then acts as a second messenger and activates another protein, usually protein kinase A, leading to cellular responses |
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other components of cAMP pathways
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• Includes G proteins, G protein-coupled receptors, and protein kinases
• The immediate effect of cAMP is usually the activation of a serine/threonine kinase called protein kinase A • The activated protein kinase A then phosphorylates various other proteins, depending on the cell type • Further regulation of cell metabolism is provided by other G protein systems that inhibit adenylyl cyclase • In these systems, a different signaling molecule activates a different receptor, which in turn activates an inhibitory G protein |
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how microbes cause disease in cholera
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• Cholera is a disease that is frequently epidemic in places where the water supply is contaminated with human feces
• People acquire the cholera bacterium, Vibrio cholerae, by drinking contaminated water • The bacteria form a biofilm on the lining of the small intestine and produce a toxin • The cholera toxin is an enzyme that chemically modifies a G protein involved in regulating salt and water secretion • Because the modified G protein is unable to hydrolyze GTP to GDP, it remains stuck in its active form, continuously stimulating adenylyl cyclase to make cAMP • The resulting high concentration of cAMP causes the intestinal cells to secrete large amounts of salts into the intestines, with water following by osmosis • An infected person quickly develops profuse diarrhea and if left untreated can soon die from the loss of water and salts |
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Viagra as a treatment
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• In one pathway, cyclic GMP acts as a signaling molecule whose effects include relaxation of smooth muscle cells in artery walls
• A compound that inhibits the hydrolysis of cGMP to GMP, thus prolonging the signal, was originally prescribed for chest pains because it increased blood flow to the heart muscle • Viagra is now widely used as a treatment for erectile dysfunction in human males because it leads to dilation of blood vessels and thus allows increased blood flow to the penis, optimizing physiological conditions for penile erections |
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calcium as a second messenger
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• Increasing the cytosolic concentration of Ca2+ causes many responses in animal cells, including muscle cell contraction, secretion of certain substances, and cell division
• In plant cells, a wide range of hormonal and environmental stimuli can cause brief increases in cytosolic Ca2+ concentration, triggering various signaling pathways, such as the pathway for greening in response to light • Cells use Ca2+ as a second messenger in both G protein and receptor tyrosine kinase pathways • Ca2+ can function as a second messenger because its concentration in the cyotosol is normally much lower than the concentration outside the cell |
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maintenance of calcium ion concentration in an animal cell
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• The level of Ca2+ in the blood and extracellular fluid of an animal is often more than 10,000 times higher than that in the cyotosol
• Calcium ions are actively transported out of the cell and are actively imported from the cytosol into the endoplasmic reticulum (and, under some conditions, into mitochondria and chloroplasts) by various protein pumps in the ER and plasma membrane driven by ATP • As a result, the calcium concentration in the ER is usually much higher than that in the cytosol • Mitochondrial pumps, driven by chemiosmosis, move Ca2+ into mitochondria when the calcium level in the cytosol rises significantly • Because the cyotosol calcium level is low, a small change in absolute numbers of ions represents a relatively large percentage change in calcium concentration • Pathways leading to calcium release involve still other second messengers, IP3 and DAG |
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inositol triphosphate (IP3)
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• A second messenger that functions as an intermediate between certain signaling molecules and a subsequent second messenger, Ca2+, by causing a rise in cytoplasmic Ca2+ concentration
• Produced by a cleavage of a certain kind of phospholipid in the plasma membrane |
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diaglycerol (DAG)
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• A second messenger produced by the cleavage of the phospholipid PIP2 in the plasma membrane
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calcium and IP3 in signaling pathways
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• Calcium ions (Ca2+) and inositol trisphosphate (IP3) function as second messengers in many signal transduction pathways
• The process is initiated by the binding of a signaling molecule to a G protein-coupled receptor • A receptor tyrosine kinase could also initiate this pathway by activating phospholipase C |
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nuclear responses to a signal: the activation of a specific gene by a growth factor
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• A representation of a typical signaling pathway that leads to the regulation of gene activity in the cell nucleus
• The initial signaling molecule, a local regulator called a growth factor, triggers a phosphorylation cascade • Once phosphorylated, the last kinase in the sequence enters the nucleus and there activates a gene-regulating protein, a transcription factor • This protein stimulates transcription of a specific gene(s) • The resulting mRNA then directs the synthesis of a particular protein in the cytoplasm |
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cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine
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• In this signaling system, the hormone epinephrine acts through a G protein-coupled receptor to activate a succession of relay molecules, including
cAMP and two protein kinases • The final protein activated is the enzyme glycogen phosphorylase, which uses inorganic phosphate to release glucose monomers from glycogen in the form of glucose 1-phosphate molecules • This pathway amplifies the hormonal signal: One receptor protein can activate about 100 molecules of G protein, and each enzyme in the pathway, once activated, can act on many molecules of its substrate, the next molecule in the cascade • The number of activated molecules given for each step is approximate |
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the mating process of yeast
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• Yeast cells are not motile; their mating process depends on the growth of localized projections of one cell toward a cell of the opposite mating type
• Binding of the mating factor causes this directional growth • When the mating factor binds, it activates signaling pathway kinases that affect the growth and orientation of cytoskeletal microfilmanets • Because activation of signaling kinases is coupled in this way to cytoskeletal dynamics, cell projections emerge from regions of the plasma membrane exposed to the highest concentration of the mating factor • As a result, these projections are oriented toward the cell of the opposite mating type, which is the source of the signaling molecule |
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how signals induce directional cell growth in yeast
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• Mark Rose sought to determine how mating factor signaling is linked to this asymmetrical growth
• Activation of Fus3, one of the kinases in the signaling cascade, caused it to move to the membrane near where the factor bound • Formin, a protein that directions the construction of microfilaments, was identified as a phosphorylation target of Fus3 kinase • The examine the role of Fus3 and formin in shmoo formation, the researchers generated two mutant yeast strains: one that no longer had the kinase and one that lacked the formin • Green-stained cells were exposed to mating factor and stained with a red fluorescent dye that labeled new cell wall growth • Concluded that the similar defect (lack of ability to form schmoos) in strains lacking either Fus3 or formin suggests that both proteins are required for schmoo formation |
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the specificity of cell signaling
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• The particular proteins a cell possesses determine what signaling molecules it responds to and the nature of the response
• The four cells respond to the same signaling molecule (red) in different ways because each has a different set of proteins (purple and teal) • The same kinds of molecules can participate in more than one pathway |
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branching of pathways
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• Often involve receptor tyrosine kinases which can activate multiple relax proteins or second messengers which can regulate numerous proteins
• Branching and "cross-talk" (Interaction) between pathways are important in regulating and coordinating a cell's responses to information coming in from different sources in the body • Moreover, the use of some of the same proteins in more than one pathway allows the cell to economize on the number of different proteins it must make |
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scaffolding protein
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• A type of large relay protein to which several other relay proteins are simultaneously attached, increasing the efficiency of signal transduction
• Have been found in brain cells that permanently hold together networks of signaling pathway proteins at synapse • This hardwiring enhances the speed and accuracy of signal transfer between cells, because the rate of protein-protein interaction is not limited by diffusion • In addition to this indirect role in activation of relay proteins, scaffolding proteins themselves may more directly activate some of the other relay proteins |
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Wiskott-Aldrich syndrome (WAS)
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• The absence of a single relay protein leads to such diverse effects as abnormal bleeding, eczema, and a predisposition to infections and leukemia
• These symptoms are thought to arise primarily from the absence of the protein in cells of the immune system • By studying normal cells, scientists found that the WAS protein is located just beneath the cell surface • The protein interacts both with microfilaments of the cytoskeleton and with several different components of signaling pathways regulating immune cell proliferation • This multifunctional relay protein is thus both a branch point and an important intersection point in a complex signal transduction network that controls immune cell behavior • When the WAS protein is absent, the cytoskeleton is not properly organized and singaling pathways are disrupted, leading to the WAS symptoms |
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termination of the signal
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• For a cell of a multicellular organism to remain capable of responding to incoming signals, each molecular change in its signaling pathway must last only a short time
• The ability of a cell to receive new signals depends on reversibility of the changes produced by prior signals • The binding of signaling molecules to receptors is reversible • As the external concentration of signaling molecules falls, fewer receptors are bound at any given moment, and the unbound receptors revert to their inactive forms • The cellular response occurs only when the concentration of receptors with bound signaling molecules is above a certain threshold • When the number of active receptors falls below that threshold, the cellular response ceases • Then, by a variety of means, the relay molecules return to their inactive forms: the GTPase activity intrinsic to a G protein hydrolyzes its bound GTP; the enzyme phosphodiesterase converts cAMP to AMP; protein phosphatases inactivate phosphorylated kinases and other proteins; and so forth • As a result, the cell is soon ready to respond to a fresh signal |
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apoptosis
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• A type of programmed cell death, which is brought about by activation of enzymes that break down many chemical components in the cell
• During this process, cellular agents chop up the DNA and fragment the organelles and other cytoplasmic components • The cell shrinks and becomes lobed ("blebbing"), and the cell's parts are package up in vesicles that are engulfed and digested by specialized scavenger cells, leaving no trace • Protects neighboring cells from damage that they would otherwise suffer if a dying cell merely leaked out all its contents, including its many digestive enzymes |
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apoptotic pathways and the signals that trigger them
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• About 15 different capases in humans and other mammals can carry out apoptosis
• The pathway that is used depends on the type of cell and on the particular signal that initiates apoptosis • One major pathway involves certain mitochondrial proteins that promote apoptosis • Surprisingly, the latter include cytochrome c, which functions in mitochondrial electron transport in healthy cells but acts as a cell death factor when released from mitochondria • Such relay proteins are capable of transducing the apoptotic signal • At key gateways int he apoptotic program, relay proteins integrate signals from several different sources and can send a cell down an apoptotic pathway • Often, the signal originates from outside the cell • When a death-signaling ligand occupies a cell-surface receptor, this binding leads to activation of capases and other enzymes that carry out apoptosis, without involving the mitochondrial pathway • Two other types of alarm signals that can lead to apoptosis originate from inside the cell rather than from a cell-surface receptor • One signal comes from the nucleus, generated when the DNA has suffered irreparable damage, and a second comes from the endoplasmic reticulum when excessive protein misfolding occurs |
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apoptosis in vertebraes
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• Essential for normal development of the nervous system, and for normal morphogenesis of hands and feet in humans and paws in other mammals
• The level of apoptosis between the developing digits is lower in the webbed feet of ducks and other water birds than in the nonwebbed feet of land birds, such as chickens • In the case of humans, the failure of appropriate apoptosis can result in webbed fingers and toes • Apoptosis is involved in degenerative diseases of the nervous system, such as Parkinson's disease and Alzheimer's disease • Also, cancel can result from failure of cell suicide; some cases of human melanoma, for example, have been linked to faulty forms of a particular protein |
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nitric oxide (NO)
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• Functions as an intercellular signal regulating blood vessel dilation and serves as a neurotransmitter
• Also involved in the immune response • Rapidly diffuses across cell membranes and stimulates the enzyme guanylate cyclase to produce cGMP • Enzyme NO synthase is responsible for synthesis |
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cyclic GMP (cGMP)
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• Mediates vasodilation
• Enzyme cGMP phosphodiesterase converts cGMP to GMP; this enzyme activates cGMP • Drugs that inhibit cGMP phosphodiesterase increase the half cGMP, thus maintaining the activity or physiological effects of cGMP |
