Cytoskeleton II

Question 1

1. Describe the three types of cytoskeletal elements, their properties, their functional roles, and their protein composition.
2. Discuss cytoskeletal dynamics and the role of certain proteins in actin filament formation, polymerization/depolymerization.
3. Describe the role of actin cytoskeleton in epithelial cell polarity and discuss some diseases associated with that.
4. Explain the concept of molecular motion, and the mechanism of actin-based organelle movement and muscle contraction.
5. Discuss the concept and the key steps of cell movement.
6. Discuss cell motility in the context of developmental and disease processes.
7. Describe the role of actomyosin ring in cell division.
8. Describe the mechanisms regulating the establishment and activation of the actomyosin ring and identify examples of asymmetric cell division.

Answer 1

x

Question 2

_____ are essential for amoeboid motility and they are structurally and functionally distinct from microtubules (MTs) and intermediate filaments.

Answer 2

Microfilaments

Question 3

There are two steps in filament formation _____, and _____. Once _____ is achieved, extension proceeds _____.

Answer 3

nucleation; extension; nucleation; rapidly

Question 4

Nucleation is catalyzed by different proteins that determine the structure of the polymerized actin

1) _____ nucleation leads to branched filaments
2) _____ nucleation leads to parallel bundles

Answer 4

1) Actin-related proteins (ARP2/3)
2) Formin

[Spontaneous nucleation does not occur (would require very high actin concentrations)]

Question 5

The microfilament polymerizes from the ____ end following nucleation

Answer 5

plus

Question 6

Over 60 accessory proteins are involved in regulating polymerization and
depolymerization:
1) _____ binds to actin and prevents polymerization
2) _______ inhibit polymerization or depolymerization, respectively
3) _____ severs actin filaments and induces depolymerization

Answer 6

1) Profilin
2) Capping proteins [cap the plus or minus ends]
3) Cofilin

Question 7

Actin bound to ATP is _____, actin bound to ADP is ____.

Answer 7

Stable; unstable

Question 8

Microvilli consist of _____, held together by cross-linking proteins (_____ and_____) and are attached to the plasma membrane by ____ and _____. Microvilli function to increase the surface area of epithelial cells for housing cell transporters. Loss of these microvilli in the small intestine leads to _______, which causes intractable diarrhea and dehydration in infants born with the disease.

Answer 8

actin bundles; villin and fimbrin; myosin-I and calmodulin; microvilli inclusion disease

Question 9

______anchors proteins involved in tight junctions and adherens junctions that hold epithelial cells together. The proteins anchored by actin in adherens junctions are ____and_____. Decreased association of actin with the adherens junction proteins leads to loss of cell-to-cell adhesion. Loss of cell adhesion, in turn, increases cell motility resulting in _______, which can cause cancer.

Answer 9

Actin; cadherins and catenins; epithelial-to-mesenchymal transitions

Question 10

Compare the attachment ratio between muscle tissue (Myosin II) and transport myosins (kinesins/dynesins).

Answer 10

Myosin II: 90% unattached, 10% attached
Transport myosin: 50%/50%

[Thick filaments have many heads, as compared to transport molecules]

Question 11

Myosin-II is the molecular motor protein responsible for muscle contraction. Myosin-II is made of a coiled-coil complex of myosin filaments. This coiled complex forms the____ filament that “walks” along actin thin filaments during muscle contraction.

Answer 11

thick

Question 12

Myosins I and V are the unconventional myosins that are associated with membranes and bind to organelles through their tails. They are responsible for moving these organelles around the cell along F- actin microfilaments. Mutations in Myosin V results in ______.

Answer 12

microvilli inclusion disease

Question 13

The power stroke of muscle contraction happens when:

Answer 13

ADP unbinds the myosin head.

Question 14

Mechanism of amoeboid locomotion:

Answer 14

1) protrusion
2) attachment
3) traction
4) detachment

Question 15

1) Protrusion: signaling from ____ and ____ causes F-actin to polymerize and form flat projections called______. Lamellipodia result from polymerization catalyzed by _____. ______ also form. They result from polymerization catalyzed by formins.

Answer 15

Rac and WASp; lamellipodia; actin-related proteins Arp2/3; Filopodia

[Filopodia also have attached receptors for “sampling” the environment in front of the cell during movement.]

Question 16

2) attachment: the _____ attach with the substratum ahead



Answer 16

lamellipodia protrusions

Question 17

3) traction: the cell is pulled forward by tension created by the ____ and _____which slide actin filaments along each other within the cell

Answer 17

anchored actin protrusions and myosin molecular motors

Question 18

4) detachment: adhesions behind the new site of anchorage are released to allow for translocation of the cell. This release is achieved through the depolymerization action of the protein _____.

Answer 18

cofilin

Question 19

Cell motility is required during development as undifferentiated cells migrate to their proper location. ____ must migrate throughout the body to give rise to pigment cells and cells of the peripheral nervous system.

Answer 19

Neural crest cells

Question 20

Cell motility also plays a significant role in disease processes and immune system response. _____ have to migrate to sites of infection in tissues from blood vessels. In cancers, cells migrate to invade healthy tissues.

Answer 20

Leukocytes

Question 21

The actomyosin ring is an actin ring structure with associated myosins that forms _____. It contracts through the action of the _____ and _____ during cytokinesis to separate the daughter cells.

Answer 21

around a dividing cell; myosin heads and ATP hydrolysis

[This is formin based. The actomyosin ring is highly regulated, so that the timing of its formation and contraction can give rise to daughter cells of varying symmetry.]

Question 22

Cells giving rise to red blood cells divide so that the nucleus is separated from the remainder of the cell. This is an example of?

Answer 22

asymmetric cell division, specifically “enucleation.”

Question 23

In platelet formation, a cell duplicates its genetic material before dividing and later divides asymmetrically many times to give rise to many cell fragments. What cell type is this, and what could be the ploidy?

Answer 23

Megakaryocyte; 128n

[Sends a finger into blood vessels, platelets are stripped off by the current]

Question 24

How do epithelial cells maintain a monolayer distribution?

Answer 24

The division of epithelial cells through a symmetric vertical axis ensures that cells maintain a monolayer distribution.

Question 25

Actin organization and, thus, cell shape are controlled, in part, by extracellular signals that act via signaling molecules. Of particular importance are molecular switches of the Rho family. These are members of the large superfamily of Ras GTPases. In their GTP-bound state they are _____, in the GDP-bound state ____.

Answer 25

active; inactive

Question 26

Changes in the actin cytoskeleton involve the function of Rho GTPases. They respond to factors that regulate random migratory activity (_____) and directed migration (____). Cells may move to attractants (____) or away from repellents (_____).

Answer 26

chemokinesis; chemotaxis; positive chemotaxis; negative chemotaxis

Question 27

Protrusion: Protrusion of fillopodia and lamellipodia is driven by polymerization of actin meshworks at the leading edge. The meshwork’s MFs have their ____ facing forward.

Answer 27

plus-ends

Question 28

Wiskott-Aldrich syndrome (WAS):
WAS is a rare, ____ immunodeficiency disease. It results from ____ mutations. Clinical symptoms include thrombocytopenia (reduced platelet number and size) and recurrent infections. WAS macrophages and neutrophil leukocytes have been shown to be _____.

Answer 28

X-linked; WASp; migration- and chemotaxis-deficient

Thrombocytopenia: [Platelets are, in essence, sloughed-off lamellipodia of megakaryocytes, so that thrombocytopenia may result from defective lamellipodia/platelet formation.]

Question 29

Lissencephaly:

This describes a severe defect of brain development resulting in _____.

Answer 29

a smooth cortical surface, i.e., the absence gyri

[Neuronal migration is a critical process for establishing the normal, complex cytoarchitecture of the brain. Loss-of-function of n-cofilin, an actin filament depolymerizing factor, results in lissencephaly and the associated severe mental retardation.]