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mcb 1 block 3 > Actin > Flashcards

Actin Flashcards

1
Q

Actin General

A

G-actin poly’s into actin filaments: F-actin to microfilaments (cytoskeleton) and thin filaments (M contract)

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2
Q

Function of Actin

A

Cell surface shape and motility, cell division and cytokinesis, Lamellipodia, filipodia, phagocytic cups, microvilli, stereocilia
Muscle contraction; vesicle and organelle mvmt

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3
Q

Describe F-actin

A

Flexible, thin, double helix, dynamic (remodeling). Polarity: (+)= fast growth (-) = slow growth

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4
Q

Actin capping

A

Actin ATP cap: stable, slowly hydro after poly, when ADP reaches end = dissoc
lvl of ATP G-actin = Rate elong/short
Increased concentration of ATP G-actin = monomers added to both ends
Decreased ATP G-actin = monomers at pos end and off neg end= treadmilling: length stable
NB: Treadmill F-actin vs Dynamic instability of MTs

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5
Q

Actin Polymerisation

A

Nucleation occurs at PM
Increased density at cell periphery = cell cortex (beneath PM) = actin filament; determines cell shape and motility
Ext signals regulate nucleation of actin filaments at PM therefore rapid changes in shape and stiffness in response to enviroment

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6
Q

Actin Nucleation 1

A

ARP 2/3 stim nucleation of G-actin: binding to form dimers and trimers (nucleus) therefore initiating polymerization.
Elongation begins: actin monomers added to nucleus or existing filament with increased affinity; ultimately form double helix (F-actin)
Monomers need bound ATP to fil/nuc
Profilin exhanges ADP for ATP, readying monomer for attach

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7
Q

F-actin Elongation

A

ARP complex binds/nucleates filamets ore efficiently when bound to side of pre-existing actin filaments (branched network)
ARP complex found at leading edge of migrating cells

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8
Q

Actin nucleation 2

A

Formins nucleate growth of straight and unbranched actin filaments
Crosslinking by other proteins to parallel bundles

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9
Q

Actin binding proteins/ Actin related proteins

A

Control filament assembly, growth, branching, capping and disassembly

  1. Cross linkers (filamin, fimbrin, villin)
  2. Severing proteins (Gelsolin, cofilin)
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10
Q

Modifications of fila elongation

A

Thymosin - Binds G-actin, prevents F-actin assembly
Profilin - binds G-actin, promotes pos end growth (ADP to ATP)
Cofilin - Promotes disassembly at pos end
Gelsolin - Caps pos end (prevents growth)

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11
Q

Regulation of actin filament organisation

A
  1. Pool of ATP-actin with profilin
  2. Signals activate WASP/Sar proteins
  3. WASP/SAR act ARP2/3 complex to initiate new filaments as branches of old
  4. Elongation
  5. Growing pushes membrane forward
  6. Cap proteins terms elongation
  7. ATP hydro and Pi dissociation
  8. ADF/Cofilin severs and depoly ADP-actin filaments
  9. LIM-Kinase inhibits ADF/cofilin
  10. Profilin catalyzes exchange of ADP for ATP
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12
Q

Myosin Motor Proteins

A

Myosin 1 - Protrusion actin rich structures (microvilli)
Myosin 2 - Contractile (M and non M)
Myosin 5 - Vesicle and organelle transport

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13
Q

Acting Organization w/in Cell

A

Bundles and weblike org, initiated by nuc protein, stab by crosslinking proteins
Stress fibers - Contractile bundle
Cell cortex - gel like network
Filopodia - tight parallel bundles

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14
Q

Actin crosslinking proteins

A

alpha actin, fimbrin, villin - parallel cables
spectrin, filamin - webs/gels
alpha action - loose bundles, stress, contract
Fimbrin - tight bundles, microvilli, non contract

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15
Q

Actin stress fibers and focal adhesions

A

Stress fibers = contractile bundles of actin filament which cross link by alpha actin
Connected to ECM at focal adhesions via integrin allowing cell to push actin network forward = mvmt

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16
Q

Microvilli

A

Fimbrin and Villin cross link, increased SA for absorb

17
Q

Stereocilia

A

Packed F-actin, non motile, Haricells ear, epididymis

18
Q

Web

A

Filamin - 3D cross links under PM = supp
Spectrin - 2D web (held by short actin filaments) under PM. To PM by ankyrin binding to band 3 (integral prot) allowing cell to deform and spring back (caps for RBC)

19
Q

Adherens Junction

A

C-C contact by cadherins (attach of actin bundles) form continuous belt of actin filaments around each epi cell

20
Q

Actin cytoskeleton attach to membrane

A

Dystrophin: anchors actin cytoskeleton to sarcolemma in skl M
Vinculin: attaches actin cyto to membrane in focal adhesion

21
Q

Actin polymerization and locomotion

A

RhoGTPase act ARP2/3 (poly at leading edge) and cofilin (depoly at trailing and reorg’s leading edge)

  1. Actin poly and branches (ARP 3/2) at lead pushes cell forward stretching actin complexes
  2. Contraction (myosin motor proteins) at rear propel body to relax tension
  3. New focal contacts (integrins bound to ECM) are made at front, old disassemble
  4. Repeat
22
Q

Contractile assembly of actin and myosin non-M

A
  1. Contract stress fibers - tension cell pulls off ECM
  2. Contract adhesion belt - alters shape of epi sheets
  3. Cytokinesis - actin filaments and myosin 2 form contractile ring under PM pinching cell in two
23
Q

Myosin 2 in M

A

Contractile activity in M and nonM. 2 ATPase heads, tail to tail interactions - large bipolar thick filaments

24
Q

Actin Thin Filament

A

F-actin capped at pos and neg end

Interacts with tropomyosin and troponin complex

25
Q

Muscle Filament

A

Thick= myosin with cross bridges
Thin = actin
Sacromere = Z to Z, M line down mid = myosin
F-actin capped = stable, cap Z pos end at Z disk, Tropomodulin in neg end
Z disk = cap Z and alpha actin

26
Q

Muscle contraction

A

N sig - act pot in M cell membrane - T-tubules (memb invag) - gap jx - sarcoplasmic reticulum - Ca release
Ca binds to troponin C, lifts toponin 1 form actin - displaces tropomyosin - myosin head binds and pulls Z disk closer = contraction

27
Q

Sliding filament mvmt

A

Myosin to pos end, ATP drives myosin power stroke, Ca influx frees myosin binding site on actin

28
Q

Wiskott Aldrich syndroe

A

X-linked immuno def, mutated WASP in haemotopoicitic cells. Fail of actin nucleation and disrupts signal path. Death before adult w/o bm transplant

29
Q

Drugs Inhibiting actin

A

Cytochalasins - binds pos end filament blocking depoly
Phalloidin - binds pos end actin blocks depoly
Latrunculin - soaks free monomers

30
Q

Rigor Mortis

A

No ATP so myosin can’t release actin therefore Ca cant be returned to SarcoRetic

31
Q

Dilated Cardiomyopathy

A

Mut=actin at bind to Z-disk - defective transmission of force in cardiac myocytes - early heart fail
Syms develop gradually - fatigue, weak, palpatations, PE and sudden death

32
Q

Familial Hypertrophic Cardiomyopathy

A

AD, myosin 2 mut, tropomyosin and troponin
Sudden death in athletes
Asym/mildly sym - dysponea, angina, palpatations, syncope, fatigue, fatal cardiac arrest

mcb 1 block 3 (18 decks)

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