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50 Cards in this Set
- Front
- Back
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What do intermediate filaments form from?
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intermediate fibrous proteins
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What do microtubules form from?
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tubulin heterodimer subunits
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What do actin microfilaments form from?
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globular actin monomers
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What is the cytoskeleton comprised of? What is it's function?
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Composition: intermediate filaments, microtubules, actin filaments
Function: mechanical support, movement of whole cells and structures within cells |
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What do intermediate filaments do?
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Cradle nucleus; provide mechanical strength to cells
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What do actin microfilaments do?
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Essential for cell movements and distribution of components at cell surface
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What do cytoskeletal filaments do?
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Operate with complementary sets of accessory proteins that confer functional diversity and regulate filament assembly
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What are the diameters of intermediate filaments? Actin? Microtubules?
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Intermediate filaments: 10 nm
Actin: 5-9 nm Microtubules: 25 nm |
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Where are intermediate filaments most abundant?
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Cells under mechanical stress
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What kind of junctions are associated with intermediate filaments?
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Desmosomal intercellular junctions
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What are the major types of intermediate filaments?
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Nuclear lamins
Cytoplasmic proteins: vimentin, desmin, glial fibrillary acidic protein, keratins, neurofilaments |
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What kind of intermediate filaments are found in breast and GI primary cancers?
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keratin positive
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What kind of intermediate filaments are found in sarcomas?
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vimentin positive
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Emery-Dreifuss Muscular Dystrophy results from what?
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Autosomal dominant mutation of genes encoding lamins A/C
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Where is Lamin-B-receptor in the nucleus?
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inner membrane
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What is the interaction between Lamins A/C and Lamin B?
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Their interaction organizes chromatin
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What depolymerizes lamins?
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phosphorylation
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What role do lamins play in mitosis?
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Reformation of nuclear membrane following mitosis
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What are the symptoms of Emery-Dreifuss muscular dystrophy?
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Progressive muscle weakness, joint contractures, cardiomyopathy
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What is the cause of epidermolysis bullosa simplex?
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Defective keratin filaments in skin epithelial cells renders them highly susceptible to mechanical rupturing producing blistering of the skin.
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How do intermediate filaments provide functional diversity to a protein?
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The variable carboxyl and amino terminal sequences allow for functional diversity.
Also, intermediate filaments have conserved alpha-helical rod domains that provide for charge bonding of subunits into dimers and tetramers. |
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What is the significance of intermediate filament subunits in nondividing cells?
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1-5% of intermediate filament protein subunits exist in a free pool and these subunits can exchange with the intermediate filament cytoskeleton
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How is a nonpolarized high-tensile strength, insoluble filament created?
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Soluble intermediate filament monomers assemble into dimers and then form staggered antiparallel tetramers which form the insoluble filament
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What mediates subunit assembly and disassembly?
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assembly: dephosphorylation
disassembly: phosphorylation |
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Where do neurofilaments cross-link?
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C-terminal extension
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What happens when a neurofilament protein mutates?
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It is a risk factor for neurodegenerative diseases, such as ALS.
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What is the relationship between globular actin (G actin) and flexible actin (F actin)?
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- G actin binds ATP
- ATP changes G actin conformation - ATP cap confers filament stability - polymerizes into F actin - F actin is polarized with a fast growing (+) end and a slow growing (-) end |
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Why is treadmilling important to actin filaments?
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Treadmilling is used by migrating cells for locomotion.
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How does treadmilling (actin) occur?
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If both ends of F actin are exposed, polymerization will proceed until [free monomers] reaches a value that is above critical concentration for the (+) end but below the critical concentration for the (-) end. At this steady state, subunits undergo a net assembly at the (+) end and a net disassembly at the (-) end at an identical rate. The microfilament will maintain a constant length, even though there is a net flux of subunits through the polymer.
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Is polymerization favored or unfavored?
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Favored in cells because free actin pool is 1000+ fold greater than the critical concentration (= 0.1 micrometers)
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What disrupts F actin?
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cytochalasin (mushroom derivative); depolymerizes F actin by binding (+) end
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What stabilizes F actin?
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phalloidin (mushroom derivative); locks subunits together
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What are the four classes of binding proteins involved in actin filament functions?
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1) regulation (thymosin beta-4, profilin, tropomodulin, capping protein)
2) severing (ADF/cofilin, gelsolin) 3) cross-linking (spectrin, dystrophin, fimbrin, filamin, alpha-actinin) 4) motor (myosin) |
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How does a cell prevent polymerization?
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thymosin binds G actin and F actin accping prevents monomer addition
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After entering the cell, how do bacteria and viruses move?
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inducing actin polymerization
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Which proteins control F actin dis/assembly?
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regulating and severing proteins
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What do cross-linking proteins do?
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They have two actin binding sites separated by divergent intervening sequences. They generate parallel and orthogonal actin arrays. Ca-2+ inhibits actin binding.
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What forms the core of microvilli?
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tight parallel bundles of microfilaments
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Make sure to look at Slide 15 and Slide 16.
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15: table of cytosolic proteins that control actin polymerization
16: cytoskeleton structure and function |
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What are the types of filament packing based on cross-linking protein length?
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- stress fiber: contractile bundle; myosin filaments intercalate and pull on F actin
- structural fiber: tight parallel bundle; tight packing for structural stability - fibroblast in vitro: stress fiber; skin wound closure - microvilli |
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What stabilizes microvilli?
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actin microfilaments and cross-linking proteins
- myosin type I, fimbrin, villin, spectrin, plectin → stabilize membrane and microvilli; ↑ surface area of absorptive cell |
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What regulates cytoplasmic fluidity?
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orthogonal cross-linking → actin gel → dissolves into sol
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Describe how actin/myosin contractile tension is carried to basal lamina.
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desmin → actin cytoskeleton → dystrophin → integral glycoproteins → laminin
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How does dystrophin stabilize skeletal muscle cell membranes?
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Links cortical F-actin cytoskeleton to basal lamina via integral membrane glycoproteins
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What happens when dystrophin is defective?
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Allows membrane tearing during contraction (e.g., muscular dystrophy)
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What is Duchenne muscular dystrophy?
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Genetic mutations alter/eliminate dystrophin binding to cortical F-actin → repeated cell membrane ruptures and muscle cell degeneration
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How are cells anchored to the extracellular matrix?
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actin microfilament linking to integral membrane glycoproteins
- migratory cells form transient focal attachments during crawling - focal contacts provide mechanical stability and signalling (FAK) |
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What roles do myosin ATPase motors play?
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1) move actin microfilaments
2) translocate vesicles along actin microfilaments 3) (+) end directed 4) myosin I binds membranes via linker proteins 5) myosin II forms thick filaments for generating actin filament sliding |
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What does amoeboid movement have to do with actin?
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The protruding edge of the crawling cell extends through dynamic assembly/disassembly of actin filaments in a branching network (dendritic nucleation model) (see slide 23 in the lecture notes (p. 52 of the notes) for more detailed mechanism)
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What is macrophage phagocytosis dependent on?
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actin-based lamellipodia formation (arrowheads)
defective phagocytosis → Wiskott-Aldrich sydnrome |
