Cytoskeleton II Flashcards
- Describe the three types of cytoskeletal elements, their properties, their functional roles, and their protein composition.
- Discuss cytoskeletal dynamics and the role of certain proteins in actin filament formation, polymerization/depolymerization.
- Describe the role of actin cytoskeleton in epithelial cell polarity and discuss some diseases associated with that.
- Explain the concept of molecular motion, and the mechanism of actin-based organelle movement and muscle contraction.
- Discuss the concept and the key steps of cell movement.
- Discuss cell motility in the context of developmental and disease processes.
- Describe the role of actomyosin ring in cell division.
- Describe the mechanisms regulating the establishment and activation of the actomyosin ring and identify examples of asymmetric cell division.
x
_____ are essential for amoeboid motility and they are structurally and functionally distinct from microtubules (MTs) and intermediate filaments.
Microfilaments
There are two steps in filament formation _____, and _____. Once _____ is achieved, extension proceeds _____.
nucleation; extension; nucleation; rapidly
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
1) Actin-related proteins (ARP2/3)
2) Formin
[Spontaneous nucleation does not occur (would require very high actin concentrations)]
The microfilament polymerizes from the ____ end following nucleation
plus
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
1) Profilin
2) Capping proteins [cap the plus or minus ends]
3) Cofilin
Actin bound to ATP is _____, actin bound to ADP is ____.
Stable; unstable
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.
actin bundles; villin and fimbrin; myosin-I and calmodulin; microvilli inclusion disease
______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.
Actin; cadherins and catenins; epithelial-to-mesenchymal transitions
Compare the attachment ratio between muscle tissue (Myosin II) and transport myosins (kinesins/dynesins).
Myosin II: 90% unattached, 10% attached
Transport myosin: 50%/50%
[Thick filaments have many heads, as compared to transport molecules]
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.
thick
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 ______.
microvilli inclusion disease
The power stroke of muscle contraction happens when:
ADP unbinds the myosin head.
Mechanism of amoeboid locomotion:
1) protrusion
2) attachment
3) traction
4) detachment
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.
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.]
2) attachment: the _____ attach with the substratum ahead

lamellipodia protrusions
3) traction: the cell is pulled forward by tension created by the ____ and _____which slide actin filaments along each other within the cell
anchored actin protrusions and myosin molecular motors
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 _____.
cofilin
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.
Neural crest cells
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.
Leukocytes
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.
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.]
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?
asymmetric cell division, specifically “enucleation.”
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?
Megakaryocyte; 128n
[Sends a finger into blood vessels, platelets are stripped off by the current]
How do epithelial cells maintain a monolayer distribution?
The division of epithelial cells through a symmetric vertical axis ensures that cells maintain a monolayer distribution.
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 ____.
active; inactive
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 (_____).
chemokinesis; chemotaxis; positive chemotaxis; negative chemotaxis
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.
plus-ends
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 _____.
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.]
Lissencephaly:
This describes a severe defect of brain development resulting in _____.
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.]
