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BMSC 220 > Topic 13: Cytoskeleton and Cell Movements > Flashcards

Topic 13: Cytoskeleton and Cell Movements Flashcards

1
Q

Cytoskeleton

A
  • consists of a network of protein filaments extending throughout the cytoplasm of all eukaryotic cells
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2
Q

Structure/Organization of Actin Filaments

A
  • Actin: predominant cytoskeleton protein of cells
  • amino acid sequence of actin are highly homologous between species
  • consists of F Actin
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3
Q

Filamentous (F) Actin

A
  • thin, flexible filaments approx. 7nm in diameter and up to several micrometers in length
  • consist of head to tail arrangement of actin monomers know as Globular (G) Actin
  • actin polymerization is reversible (non-covalent)
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4
Q

Actin Filaments

A
  • microfilaments
  • traverse throughout the cytoplasm of a cell
  • pointed end = neg. end
  • barbed end = + end
  • -> rapid monomer addition
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5
Q

Globular Actin

A
  • an actin monomer that has tight binding sites that mediate head-to-tail interactions with other actin monomers
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6
Q

Filamentous Actin

A
  • a series of actin monomers that have been polymerized into filaments (helical structure)
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7
Q

Polymerization

A
  • reversible
  • filaments can depolymerize by the dissociation of actin subunits, allowing actin filaments to be broken down when necessary
  • can happen without ATP
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8
Q

Role of ATP in Microfilament Polymerization

A
  • polymerization occurs faster
  • ATP-actin = associates with filaments more readily than ADP-actin
  • ADP-actin = dissociates from filaments more readily than ATP-actin
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9
Q

Treadmilling

A
  • occurs in vitro at equilibrium rate of addition and removal of monomers
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10
Q

Monomer Association/Dissociation In Vivo in Cytoplasm

A
  • critical for formation of cell projections and cell movement
  • regulated by actin-binding proteins in vivo, such that stability/instability of actin filaments can vary tremendously depending on cell need
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11
Q

Initiation of Actin Filaments

A
  • initial polymerization of 3 actin monomers is rate limiting step
  • catalyzed by FORMIN
  • PROFILIN stimulates the exchange of ADP for ATP
  • -> associated with formin
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12
Q

Branching of Actin Filaments

A
  • Formin and Arp 2/3 complex add actin monomers to the barbed end of actin chain
  • causes branching
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13
Q

Higher Order Actin Filament Organizations

A
  1. Actin Network

2. Actin Bundles

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14
Q

Actin Network

A
  • the actin filaments are cross-linked in orthogonal arrays that form 3D meshwork’s with the properties of semisolid gels
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15
Q

Actin Bundles

A
  • actin filaments are cross-linked into closely packed arrays
  • ex) microvilli in intestinal epithelial cells contain parallel arrays of actin filaments
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16
Q

Actin-Bundling Proteins

A
  • small rigid proteins that force the cross-linked actin filaments to align closely with one another in bundles
  • alpha actinin, fimbrin
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17
Q

Alpha Actinin

A
  • in contractile bundles

- bundles are more widely spaced to allow for contraction

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18
Q

Fimbrin

A
  • in non-contractile bundles
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19
Q

Actin-Network Forming Proteins

A
  • have 2 flexible arms that interact with separate actin filaments
  • ex) filamin
  • forms a mesh like structure
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20
Q

Glycophorin

A
  • associated with actin cytoskeleton network immediately underlying plasma membrane
  • spectrin and actin together form the cortical cytoskeleton
  • ex) red blood cell cortical cytoskeleton
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21
Q

Microvilli

A
  • fingerlike extensions of the plasma membrane
  • abundant on the surface of cells
  • involved in absorption
  • epithelial cells lining the intestine
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22
Q

Actin-Filaments in Cell-ECM Associations

A
  • most cells have specialized regions of p. membrane that form contacts with adj. cells (ECM) or other substrata
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23
Q

Stress Fibres

A
  • bundles of contractile actin filaments in many cell types

- allow cell to exert force against the substratum through cell-extracellular matrix junctions

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24
Q

Actin Microfilaments

A
  • determination of cell shape
  • providing structural support
  • important role in formation of cell projections and cell motility
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25
Q

Cell Migration Requires

A
  1. Actin cytoskeleton growth and branching at leading edge (actin-binding proteins)
  2. Dissociation of focal adhesions at trailing edge and formation of new focal adhesions at leading edge
  3. Actin cytoskeleton contraction at trailing edge (actin/myosin interaction)
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26
Q

Myosin

A
  • a protein that interacts with actin

- acts as a molecular motor

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27
Q

Molecular Motor

A
  • a protein that converts chemical energy in the form of ATP to mechanical energy
  • generating force and movement
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28
Q

Contractile Properties

A

Actin-Myosin Interactions

29
Q

Types of Myosin

A
  • several diff. types depending on cell type
  • all are polarized molecules with structurally and functional distinct head and tail regions
  • Myosin head acts as hinge that pulls along actin filaments
30
Q

Cell Migration

A
  • actin filament contraction
  • action of polymerization/branching and retraction of trailing edge through actin depolymerization
  • -> cell “pulls” itself” forward at focal adhesions
31
Q

Components necessary for remodelling

A
  • Rho stimulates WASP proteins which stimulate Arp2/3 complex
  • Rho stimulates formin and profiling
32
Q

Cofilin

A
  • actin binding proteins
  • severs existing actin filaments
  • result in growth of 2 filaments from an existing one
33
Q

Actin Polymerization and Remodelling

A
  • response to cell signalling from other cells or the environment
34
Q

Intermediate Filaments

A
  • providing mechanical strength to cells and tissues
  • form a scaffold to assist in localization of cell process
  • essential for maintaining tissue organization and mitigating the impact of external forces on cell sheets
35
Q

Keratins

A
  • type of intermediate filament protein of epithelial cells
36
Q

Vimentin

A
  • forms a network extending out from the nucleus toward cell periphery
37
Q

Desmin

A
  • specifically expressed in muscle cells

- connects contractile elements

38
Q

Neurofilament Proteins

A
  • form major intermediate filaments of many types of mature neurons
39
Q

Structure of IFs

A
  • central alpha helical rod
    N terminus (head)
    C terminus (tail)
  • no polarity
40
Q

Plakins

A
  • a family of proteins that bind intermediate filaments and link them to other cellular structures
  • ex) cadherins, desmoglein and desmocollin (desmosome)
41
Q

Plectin

A
  • also a type of plakin that links IFs to interns of hemidesmosome
42
Q

Microtubules

A
  • rigid hollow rods
  • determine cell shape
  • involved in a variety of cell movements
43
Q

Tubulin

A
  • protein that polymerizes to form microtubules
  • 1 alpha + 1 beta isoform = tubulin dimer
  • have polarity
44
Q

GTP in Microtubule Polymerization

A
  • GDP bound tubulin readily dissociate from minus end (must be protected in cell)
45
Q

Dynamic Instability

A
  • behavior in which individual microtubules alternate between cycles of growth and shrinkage at the plus end
  • Dependent on rate of GTP hydrolysis at plus end of microtubule, and free pool of GTP bound tubulin dimers
46
Q

Colchicine and Colcemid

A
  • experimental drugs

- bind tubulin and inhibit microtubulin polymerization (blocks mitosis)

47
Q

Vincristine and Vinblastine

A
  • drugs used in chemotherapy

- inhibit microtubule polymerization (blocks mitosis)

48
Q

Taxol

A
  • a drug that stabilizes microtubules

- blocks cell division

49
Q

3 Categories of MAPs

A
  1. growth (polymerase)
  2. Shrinkage or catastrophe (depolymerase)
  3. Rescue (CLASP protein)
50
Q

Centrosome

A
  • the microtubule-organizing center in animal cells
  • anchoring point of minus end of most microtubules
  • initiates microtubule growth
51
Q

Structure of Centrosomes

A
  • pair of centrioles anchored perpendicular to each other within amorphous pericentriolar material
  • pericentriolar material initiates microtubule assembly
52
Q

Kinesins

A
  • motor proteins that move along microtubules toward plus end and minus end
  • depends on cell type and cargo
  • specific kinesin involved
53
Q

Dyneins

A
  • motor proteins that move along microtubules only toward minus end
54
Q

Head Region

A
  • microtubule interaction (motor) domain
  • position along N-terminal/C-terminal length
  • determines direction
55
Q

Tail Regions

A
  • cargo/organelle interaction domain

- specificity determined by primary amino acid sequence and 2nd structure

56
Q

Axoneme

A
  • the fundamental structural unit of organization of both cilia and flagella
  • composed of microtubules and their associated proteins
57
Q

Basal Body

A
  • structure similar to a centriole that initiates the growth of axonemal microtubules
  • anchors cilia and flagella to the rest of the cell
58
Q

Cross-Sectional Structure of Cilia and Flagella

A

9+2 pattern

59
Q

Cilia and Flagella Movement

A
  • dynein is responsible for movement
  • result from the sliding of outer microtubule doublets
  • powered by motor activity of axonemal dyneins
  • requires precise coordination
60
Q

Microtubules during Mitosis

A
  • centrioles and other components of the centrosome are duplicated
  • move to opposite poles
  • mitotic spindles are responsible for separating daughter chromosomes
  • Dynamic instability of microtubules is very important for the mitotic process
61
Q

mitotic spindles

A
  • array of microtubules extending from the spindle poles
62
Q

Kinetochore Microtubules

A
  • attach to the condensed chromosomes of mitotic cells at their centromeres
63
Q

Chromosomal Microtubules

A

connect to the ends of the chromosomes via chromokinesin

64
Q

Astral Microtubules

A
  • extend outward from the centrosomes to the cell periphery and contribute to chromosome movement by pushing the spindle poles apart
65
Q

Polar Microtubules

A
  • are not attached to chromosomes but are stabilized by overlapping with each other in the center of the cell
  • contribute to chromosome movement by pushing the spindle poles apart
66
Q

Anaphase A

A
  • movement of chromosomes toward the spindle poles along the kinetochore microtubules
  • chromosomal and kinetochore
67
Q

Anaphase B

A
  • separation of spindle poles themselves

- polar and astral

68
Q

Chromosome movement

A
  • requires minus-end motor proteins and microtubule disassembly
69
Q

Spindle Pole Separation Requires

A
  1. pulling action of astral microtubules directed by minus-end directed motor proteins anchored to distal region of the cell
  2. sliding of polar microtubules past each other due to action f +end directed motor proteins

BMSC 220 (6 decks)

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