Term
|
Definition
| microfilaments [actin], microtubules [tubulin] and intermediate filaments |
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Term
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Definition
| smallest, most dynamic of cytoskeletal structure (though with muscle, stable). 6nm in diameter. enriched in cell cortex. |
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Term
| microfilament Actin filament have a fast and growing side, which is which? |
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Definition
| barbed-end = fast, pointed [arrow] end = slow |
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Term
| Microfilaments in most cells most likely to be found? |
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Definition
| at the periphery to form the membrane cytoskeleton [but can be found through the cytoplasm] |
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Term
| Type of actin and location? |
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Definition
| alpha = skeletal muscle, Beta/gamma = muscle and nonmuscle cells (6 actin genes in 3 families) |
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Term
| Describe the actin protein (molecular shape) |
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Definition
| 43kDA globular protein, 375AA with two domains surrounding a nucelotide binding pocket |
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Term
| ATPase activity in microfilaments |
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Definition
| hexokinase and heat shock protein (hsp70); hexokinase is an enzyme that phosphorylates a six-carbon sugar, a hexose, to a hexose phosphate |
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Term
| example of actin as a stabilizing filament? |
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Definition
| tropomyosin - binds to groove of MF |
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Term
| example of actin as a bundle/cross link filament? |
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Definition
| fibrin or alpha actinin link adjacent filaments into a bundle, whereas filamin links create actin MF gels |
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Term
| actin can become a fragment filament when? |
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Definition
| gelsolin seves filaments into shorter filaments |
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Term
| actin can be attached to a membrane when? |
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Definition
| spectrin anchors filaments to membrane surfaces by binding MFs and membrane proteins |
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Term
| atin bins monomers and regulates actin polymerization when? |
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Definition
| profilin binds soluble g-actin monomers, but in response to signals can release actin for rapid polymerization |
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Term
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Definition
| proteins involved in regulating cell shape, adhesion and motility in actin - capping proteins increase actin microfilament dynamics |
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Term
| Microfilament function - structural and motile |
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Definition
| membrane cytoskeleton, vesicle movement [secretion], cytokinese, cell locomotion, cell shape, cell adhesion, muscle contractility, metabolic compartmentation |
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Term
| Phallotoxins from deadly Amanita phalloides mushrooms |
|
Definition
| bind and stabilize F-actin |
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Term
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Definition
| - toxic isolated from a Red Sea Sponge, disrupts MF organization in cultured cells |
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Term
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Definition
| family of fungal metabolites that bind to fast growing, barbed end of MF to block assembly and disassemble at that end |
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Term
| Pathogens exploit ____ due to its motility to spread and move within the cells |
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Definition
| actin, microfillaments - ex. Listeria and Shigella - bacteria. Vaccinia - virus |
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Term
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Definition
| genetic disease, mutated WASP protein doesn't have rapid assembly of actin filaments; defect in cellular immunity, lymphoid development, muturation/function of myeloid monocytic cells |
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Term
| Cardiomyopathy [Familial hypertrophic Cardiomyopathy or Idiopathic Dilated cardiomyopathy] |
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Definition
| genetic disease, altered organization of actin cytoskeleton due to mutations in alpha cardiac actin. FHC effects contraction, IDC forces transmission fromt he sarcromere. overall, loss of fibrils |
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Term
|
Definition
| oncogenes that modulate actin cytoskeleton, |
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Term
| Celiac disease [cytoskeletal role] |
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Definition
| actin filaments are a common autoantigen [so abundent] |
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Term
|
Definition
| actin-specific drug, severs filaments |
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Term
|
Definition
| polymer of 50kD tubulin subunit, heterodimers of alpha and Beta-tubulin align end to end in protofilaments, 13 joint laterally form a hollow tube with an outer diameter of 25nm [sometimes 12 or 14 or 15 protofilaments] |
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Term
| walls of cytoplasmic MT structure |
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Definition
| series of linear polymers of tubulin alpha-beta dimers known as protofilaments, in typical MT 13 protofilmanets arranged side by side to form the wall of the tubule. |
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Term
|
Definition
| few micrometers to hundreds of micrometers |
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Term
| basal bodies and centrioles structure |
|
Definition
| 9 sets of circumferentially arranged triplet microtubules. |
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Term
| triplet microtubules structure |
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Definition
| paired structures with two cylinders orientated orthogonally to each other |
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Term
| cilia and flagellae grow directly out of ____ |
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Definition
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Term
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Definition
| surrounds centrioles, this is where the cytoplasmic and mitotic spindle microtubules nucleate by rings of gamma-tubulin. |
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Term
| microtubule organizing centers |
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Definition
region where cytoplasmic and mitotic spindle MT nucleate by rings of gamma-tubulin; serve to nucleate and organize
cytoplasmic microtubules. The minus ends are anchored at the MTOC, generating a polarity for cytoplasmic |
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Term
|
Definition
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Term
|
Definition
| 9 sets of circumferentially arranged doublet microtubules plus a pair of centrally located single MTs. |
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Term
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Definition
| in free-swimming cells - ex. sperm |
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Term
|
Definition
| cells which are part of solid tissue |
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Term
| Dynein-induced MT sliding |
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Definition
| Allow cilia and flagella to beat/gyrate |
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Term
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Definition
| subunit of MT; popypeptide subunit of ~50kD but must form stable heterodimers. tubulin is highly conserved; only alpha-beta heterodimers are present in MT proper. |
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Term
| Tubulin dimers structure? |
|
Definition
| contain two guanine nucleotides |
|
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Term
| structure of Tubulins and GTPases? |
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Definition
| beta tubulin GTp = readily exchangable and hydrolyzes. Alpha = poorly exchangable. GTP form of tubulin dime wants assembly at plus end, GDP wants disassembly |
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Term
| Microtubule-associated proteins (MAPs) function |
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Definition
| stimulate MT assembly and stabilization, link MTs to other cellular structures and serve as scaffolds for proteins [kinases and phosphatases] |
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Term
| Major types of MAPs? (Microtubule-associated proteins) |
|
Definition
| 1. tau - in brain - 60-70kD, 2. MAP1 and MAP2 [250kD] and MAP4 in nonneuronal cells, type 1 - MAP1 = m=terminal MT binding domain. type 2 MAPs[tau, MAP2, MAP4] have a c-terminal MT binding domain - 18 AA repeat. basic. |
|
|
Term
acetylation or
detyrosination |
|
Definition
| MT modifying protein, introduces posttranslational modifications to tubulin |
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Term
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Definition
| MT modifying protein, cleaves MT |
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Term
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Definition
| interphase [transports membrane-bound organelles, determination of cell polarity and shape, consolidation of cell movement], mitosis and meiosis [spindles, segregation of chromosomes - karyokinesis]. |
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Term
|
Definition
| 1. prophase, 2. metaphase, 3. anaphase, 4. telophase, |
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Term
|
Definition
nuclear membrane breakdown and
chromosome condensation |
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Term
|
Definition
formation of spindle; chromosomes align at
center of the spindle |
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Term
|
Definition
|
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Term
|
Definition
| cleavage furrow forms, and cytokinesis occurs; nuclear membranes form around newly formed daughter nuclei |
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Term
|
Definition
| MT destabilizing drug [treat cancer] |
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Term
|
Definition
| MT stabilizing drug [treat cancer] |
|
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Term
|
Definition
| Tau aggregates form neurofibrillary tangles, increase density correlate with dementia |
|
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Term
| Frontotemporal dementia and parkinsonism (FTDP-17) |
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Definition
| mutation in gene for MAP tau |
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Term
| Hereditary Spastic Paraplegia: |
|
Definition
| gene most frequently mutated in HSP is spastin, a protein that can fragment microtubules. |
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Term
|
Definition
| protein that can fragment microtubules. |
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Term
| Mutations in Lis1 (Lissencephaly) |
|
Definition
| Doublecortin or tubulin alpha 1a produce alterations in cortical layering due to altered neuronal migration |
|
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Term
| Mutations in Beta3 tubulin |
|
Definition
| produce cogenital fibrosis of the extraocular muscles type 3 and may lead to cognitive and behavioral disorders, facial paralysis and a late onset sensory polyneuropathy [droping eyes syndrome] |
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Term
| Actin is a 1. ATPase or 2. GTPase |
|
Definition
| ATPase, tubulins are GTPases |
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Term
|
Definition
| the nucleus, where MTs are usually found. orientated away from the center towards periphery(at the + side). - end near center. |
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Term
|
Definition
| binds tubulin dimers to affect MT dynamics |
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Term
| dynein [involved with MT] |
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Definition
|
|
Term
| kinesin [involved with MT] |
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Definition
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Term
| Intermediate filaments structure? |
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Definition
| 10nm in diameter and 10-100micrometers long, forms a nuclear envelope in all nucleated cells, but cytoplasmic forms not found in plants,lower euks; expression cell-type specific |
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Term
|
Definition
| type 1 and II, found in epithelial cells |
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Term
| IF protein vimentin, acidic proteins and desmins, glial fibrillary |
|
Definition
| Type III, vimetin [found in fibroblasts], glial fibrillary, acidic proteins [astrocytes], desmin [smooth muscle cells] |
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Term
| IF protein Neurofilaments |
|
Definition
| Type IV, found in all vertebrate nuerons |
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Term
|
Definition
| Type V, found in nuclear envelope |
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Term
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Definition
| IF associatiated protein, is alternatively spliced |
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Term
|
Definition
| IF associated protein, 230kD, epithelial cells binds keratin filaments to hemidesmosomes, mutants cause a blistering disease |
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Term
|
Definition
| IF associated protein, 280kD, sensory neurons crosslink neurofilaments to membrane cytoskeleton, mutants have an axonopathy |
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Term
|
Definition
| IF associated protein, 37kD cornified epithelia aggregates keratin |
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Term
| Lamin-associated proteins |
|
Definition
| IF associated protein, 57-75kD nuclear envelope |
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Term
|
Definition
| IF associated protein, 34kD, inner nuclear membrane mutants develop Emery-Dreifuss muscular dystrophy |
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Term
|
Definition
IF associated protein, 500kD homodimer, links keratin to other cytoskeletal elements, mutant causes
blistering disease |
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Term
|
Definition
1. most cell-specific of cytoskeletal elements
2. are flexible even when bundled
3. are the most stable cytoskeletal structures
4. provide mechanical strength to cells, tissue, & extracellular structures (i.e. hair)
5. have structural, but not motile functions
6. major protein component of skin & hair
7. contribute to cell interactions through desmosomes and hemidesmosomes
8. form nonpolar filaments. |
|
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Term
| Epidermolysis Bullosa Simplex |
|
Definition
| diseases of skin blistering: IF disease due to keratins |
|
|
Term
| Amyotrophic Lateral Sclerosis |
|
Definition
| exhibit accumulations of neurofilaments in the initial segment of the axon. Mutations in neurofilaments may be associated with some forms of ALS-like motor neuron disease or some forms of Charcot-Marie-Tooth peripheral neuropathies |
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Term
|
Definition
|
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Term
|
Definition
| premature aging, IF lamina disease |
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Term
| muscle myosin (myosin IIs) and flagellar dyneins |
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Definition
| two types of molecular motors |
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Term
| 3 superfamilies of the molecular motors |
|
Definition
| myosins (>18 gene families) that move along microfilaments; the dyneins (16 genes) and the kinesins (>45 genes) both of which move along microtubules |
|
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Term
| how can you differentiate myosins and dyneins |
|
Definition
| pharmacologically by differential susceptibility to inhibitors ATPase activity |
|
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Term
| what first provided the first indication of a molecular motor? |
|
Definition
| muscle [myosin] - later brain then other cells |
|
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Term
|
Definition
| you can observe enormous amount of vesicle transport along MTs [fast axonal transport]. When inhibitors applied, didn't match myosin or dynein motors |
|
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Term
| adenylylimidodiphosphate (AMP-PNP) |
|
Definition
| a weak competitive inhibitor of both myosin and dynein, requiring a 10-100 fold excess of analogue. But with giant squid fast axons, within minutes of this drug, both anterograde and retrograde axonal transport stops; inhibition by this drug occurs in prsences of stoichiometric concentrations of ATP. discovered kinesins! |
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Term
|
Definition
| MT based motor, inhibited by AMP-PNP |
|
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Term
| sea urchin sperm flagella first isolated what? |
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Definition
| dyneins [cilia and flagella - cilium type] |
|
|
Term
| three different sets of proteins were bound to MTs in the absence of ATP and released from MT by addition of ATP |
|
Definition
1. Kinesin
2. previously called MAP1c (protein) - dynein heavy chain [found in cytoplasm - not cilia]
3. dynamin [not a motor at all, a GTP binding protein important for endocytosis ] |
|
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Term
|
Definition
| Not an MT motor protein, a GTP binding protein important to endocytosis |
|
|
Term
| Presence of ATP on MT bound proteins ______ and absence of ATP ______ |
|
Definition
| releases, and binds (no ATP - think of rigor mortis] |
|
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Term
|
Definition
| all actin based motor proteins (myosin II, muscle and nonmuscle, and moving organelles and other cargo on MF) |
|
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Term
|
Definition
| slides antiparralllel MFs past each other |
|
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Term
| number of types of myosin |
|
Definition
| 18 - all heavy chains share homology and interact with MFs |
|
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Term
|
Definition
| monomeric myosin, interacts with membranes. important in endocytosis, plays a role in hearing and balance by interacting with the mechanosensory channels in hair cells in acousticovestibular system] |
|
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Term
|
Definition
| most familiar form of myosin, includes all the muscles myosins and found in nonmuscle cells too [dimer of two heavy chains with 2-4 accessory subunits], important in cell locomotion and cytokinesis |
|
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Term
|
Definition
found in many tissue types, plays a role in delivery vesicles to PM.
2. Also a dimer of two heavy chains with multiple associated calmodulin molecules acting as regulatory subunits.
3. also bind to vesicles that interact with kinesin |
|
|
Term
|
Definition
1. cell motility
2. cytokinesis
3. structural support [microvilli, sterocilla]
4. membrane cytoskeleton |
|
|
Term
| Mysoin and cell motility still need |
|
Definition
| MT [required for guidance, can't have cell motility without] |
|
|
Term
| MFs at the leading edge of a moving cell may form ______ or _______ |
|
Definition
| thin spikes (filopodia) or broad sheets (lamellopodia) -- by combination of actin assembly and myosin motor actin |
|
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Term
|
Definition
| thin spikes [MF changes in cell motility] |
|
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Term
|
Definition
| broad sheets [MF changes in cell motility] |
|
|
Term
| what occurs in cytokinesis? |
|
Definition
| MF form a contractile ring that constricts cytoplasm between newly forming daughter cells after teolphase. Myosin contribues to tthis assembly and contraction of contractile rings |
|
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Term
|
Definition
| MF align in parallel occupying the core of each; forming a brush border of dozen of these at the apical surfaces. |
|
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Term
|
Definition
| have a narrower at the base than at the distal tip; found at apical surfaces of epithelial cells localed in the epididymis and inner ear [sound waves] |
|
|
Term
| Diseases associated with myosin? |
|
Definition
1. Griscelli syndrome
2. Usher syndrome
3. Snell's Walzer mouse - mutation in myosin VI [vestibular defects] |
|
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Term
|
Definition
| rare inherited disease characterized by immunodeficiency and partial albinism, sometimes with a neurological component that can be due to Myosin V mutations. Myosin V plays a key role in delivery of pigment granules from melanosomes to hair follicles. Defects in this form myosin V lead to a silvery grey color of hair because kinesin I delivers the pigment to the cell periphery, but myosin V is needed to pass through the membrane cyoskeleton. |
|
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Term
|
Definition
| a set of autosomal recessive diseases with sensorineural hearing loss and retinitis pigmentosa. Type 1 Usher syndrome may be due to mutation in an unconventional myosin (myosin VII). |
|
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Term
|
Definition
| flagellar and cilia motor cells, greater than 10^6 Daltons in size; in flagellar: 2 or 3 heavy chains (over 500kD), 3 75kD intermediate chains and a variable number of light chains (8-24kD). |
|
|
Term
| structure/composition of cilia and flagella |
|
Definition
| distinct bundled set of MT based structures covered by the plasma membrane; cells with single motile [sperm] = flagellum, cells with multiple cilia = cilia. except nonmotile cilium from centriole. All cilia originate from a modified centriolar structure [basal body]. |
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Term
|
Definition
| 9 triple Ms arranged in a ring that forms the base of ciliary MT; as MT goes upward, covert 9 doublets MTs crosslinked [and in motile cilia, a pair of singlet MTs originates in the center of the cilium] |
|
|
Term
| how flagellar dyneins work |
|
Definition
| MTs slide relative to each other to allow for flagella beating; when ATP added, MTs slide past each other |
|
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Term
|
Definition
| heavy chain, centrally located |
|
|
Term
| Number of ATP binding sites in myosin, kinesin and dynein |
|
Definition
1 ATP binding site = myosin, kinesin
4-5 atp = Dynein heavy chain [not all functional] |
|
|
Term
| dynein heavy chain specialized structure? |
|
Definition
| specialized loop that forms the MT binding domain |
|
|
Term
| Dynein intermediate chains important for? |
|
Definition
| important for the interactions between dynein and other structures inclyding dynactin and membranes |
|
|
Term
| dynein light chain plays a role in? |
|
Definition
| binding to different cargos or in regulation of dynein motility |
|
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Term
|
Definition
| 14 different dynein heavy chain genes expressed and present in a single cilium. each subunit of flagellar on any organism can be multigene families. |
|
|
Term
|
Definition
| discovered cytoplasmic dyneins because of it - both myosin and dyneins MAP1C are found and both are released by ATP. dynein move MT in vitro with a polarity opposite of that seen with kinesin, and was IDed as a two headed cytoplasmic dynein |
|
|
Term
|
Definition
| form a 40nm long two headed complex weighing 1.6^6D. includes two heavy chains, and light and intermediate MW chains. |
|
|
Term
| cytoplasmic dyneins found? |
|
Definition
| at mitotic spindles, interphase cells [bound to organelles]. important role in assembly and orientation of mitotic spindles |
|
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Term
|
Definition
| 106D structure, some cyto dyneins require interaction with this multiprotein complex. is a linker between cytoplasmic dynein and some other structure [centrosomal material, actin cytoskeleton, membranes] |
|
|
Term
|
Definition
| Dynactin subunits include: 8 or 9 Arp1 (actin-related protein 1); 4 or 5 dynamitin; 2 p150 Glued; 2 p24; one each of p62, conventional actin, Arp11, capping protein a and b, p27 and p25. |
|
|
Term
| Dynactin interactions with dynein is found on it where? |
|
Definition
| dynein intermediate chains, p150 Glued, and dynamitin; regulated by phosphorylation. |
|
|
Term
| diseases associated with dynein? |
|
Definition
1. spinal musclar atrophy
2. ALS-like motor neurons - mutations in dynactin
3. Lissencephaly
4. Situs Inversus
5. syndromic male sterility |
|
|
Term
|
Definition
| could be a dynein disease, related to mutation in dynein heavy chain gene |
|
|
Term
|
Definition
severe brain developmental defect due to mutations in a dynein associated protein known as Lis1, which is thought to play a role in anchoring dyneins to specific locations during cell divisions and embryonic development. As a result of mutations in this gene, neuronal cells fail to migrate properly and the complex layering of the cortex fails to form,
leading to severe retardation and early death. Brains of patients with lissencephaly have a smooth
cortex, lacking the various folds and ridges characteristic of a normal brain. |
|
|
Term
|
Definition
Reversal or randomization of normal organ locations (i.e heart on right
instead of the left side of the chest) Associated with mutations in flagellar dyneins or kinesin related motor proteins. |
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