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

Topic 13: Cytoskeleton and Cell Movements Flashcards

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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
Cell Migration Requires
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)
26
Myosin
- a protein that interacts with actin | - acts as a molecular motor
27
Molecular Motor
- a protein that converts chemical energy in the form of ATP to mechanical energy - generating force and movement
28
Contractile Properties
Actin-Myosin Interactions
29
Types of Myosin
- 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
Cell Migration
- actin filament contraction - action of polymerization/branching and retraction of trailing edge through actin depolymerization - -> cell "pulls" itself" forward at focal adhesions
31
Components necessary for remodelling
- Rho stimulates WASP proteins which stimulate Arp2/3 complex - Rho stimulates formin and profiling
32
Cofilin
- actin binding proteins - severs existing actin filaments - result in growth of 2 filaments from an existing one
33
Actin Polymerization and Remodelling
- response to cell signalling from other cells or the environment
34
Intermediate Filaments
- 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
Keratins
- type of intermediate filament protein of epithelial cells
36
Vimentin
- forms a network extending out from the nucleus toward cell periphery
37
Desmin
- specifically expressed in muscle cells | - connects contractile elements
38
Neurofilament Proteins
- form major intermediate filaments of many types of mature neurons
39
Structure of IFs
- central alpha helical rod N terminus (head) C terminus (tail) - no polarity
40
Plakins
- a family of proteins that bind intermediate filaments and link them to other cellular structures - ex) cadherins, desmoglein and desmocollin (desmosome)
41
Plectin
- also a type of plakin that links IFs to interns of hemidesmosome
42
Microtubules
- rigid hollow rods - determine cell shape - involved in a variety of cell movements
43
Tubulin
- protein that polymerizes to form microtubules - 1 alpha + 1 beta isoform = tubulin dimer - have polarity
44
GTP in Microtubule Polymerization
- GDP bound tubulin readily dissociate from minus end (must be protected in cell)
45
Dynamic Instability
- 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
Colchicine and Colcemid
- experimental drugs | - bind tubulin and inhibit microtubulin polymerization (blocks mitosis)
47
Vincristine and Vinblastine
- drugs used in chemotherapy | - inhibit microtubule polymerization (blocks mitosis)
48
Taxol
- a drug that stabilizes microtubules | - blocks cell division
49
3 Categories of MAPs
1. growth (polymerase) 2. Shrinkage or catastrophe (depolymerase) 3. Rescue (CLASP protein)
50
Centrosome
- the microtubule-organizing center in animal cells - anchoring point of minus end of most microtubules - initiates microtubule growth
51
Structure of Centrosomes
- pair of centrioles anchored perpendicular to each other within amorphous pericentriolar material - pericentriolar material initiates microtubule assembly
52
Kinesins
- motor proteins that move along microtubules toward plus end and minus end - depends on cell type and cargo - specific kinesin involved
53
Dyneins
- motor proteins that move along microtubules only toward minus end
54
Head Region
- microtubule interaction (motor) domain - position along N-terminal/C-terminal length - determines direction
55
Tail Regions
- cargo/organelle interaction domain | - specificity determined by primary amino acid sequence and 2nd structure
56
Axoneme
- the fundamental structural unit of organization of both cilia and flagella - composed of microtubules and their associated proteins
57
Basal Body
- structure similar to a centriole that initiates the growth of axonemal microtubules - anchors cilia and flagella to the rest of the cell
58
Cross-Sectional Structure of Cilia and Flagella
9+2 pattern
59
Cilia and Flagella Movement
- dynein is responsible for movement - result from the sliding of outer microtubule doublets - powered by motor activity of axonemal dyneins - requires precise coordination
60
Microtubules during Mitosis
- 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
mitotic spindles
- array of microtubules extending from the spindle poles
62
Kinetochore Microtubules
- attach to the condensed chromosomes of mitotic cells at their centromeres
63
Chromosomal Microtubules
connect to the ends of the chromosomes via chromokinesin
64
Astral Microtubules
- extend outward from the centrosomes to the cell periphery and contribute to chromosome movement by pushing the spindle poles apart
65
Polar Microtubules
- 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
Anaphase A
- movement of chromosomes toward the spindle poles along the kinetochore microtubules - chromosomal and kinetochore
67
Anaphase B
- separation of spindle poles themselves | - polar and astral
68
Chromosome movement
- requires minus-end motor proteins and microtubule disassembly
69
Spindle Pole Separation Requires
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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