Cytoskeleton

Question 1

What holds filaments together?

Answer 1

Weak non-covalent interactions

Question 2

What shape do filaments usually have?

Answer 2

Helices joined together laterally.

Question 3

What are 3 major roles of microtubules?

Answer 3

1. Organelle transport (tracks)
2. Cilia and flagella
3. Cell division

Question 4

Describe the microtubule structure.

Answer 4

2 tubulin subunits: alpha and beta forma hetrodime

Question 5

How do microtubules grow?

Answer 5

MTOC nucleate the growth at the minus end with the plus end growing away from it. Facilitated by MAPS (e.g. Tau).

Question 6

What drugs affect microtubule function?

Answer 6

KN_ [Taxol (binds and occupies)
Colchicine (prevents polymerization)
Vinblastine (prevents polymerization)

Question 7

What roles do actin play?

Answer 7

1. Cell shape
2. Cell locomotion
3. Cytokinesis
4. Phagocytosis
5. Platelet aggregation

Question 8

What are the 6 classes of intermediate filaments?

Answer 8

1. Lamins
2. Keratins
3. Neurofilaments
4. Vimentins
5. GFAP (glia)
6. Desmin

Question 9

What are the 3 steps of cell movement?

Answer 9

1. Protrusion of the leading edge
2. Adhesion of the leading edge/deadhesion of trailing edge
3. Movement of the cell body

Question 10

What structure operates at the protruding edge of actin cytoskeletons?

Answer 10

Lamellipodia, thin sheet-like projections that pull cells through tissues.

Question 11

What is behind the lamellipodia?

Answer 11

A more stable region of lamella which couples the actin network to myosin II-mediated contractility substrates (e.g. ECM of another cell)

Question 12

What severs the ends of existing actin filaments in response to growth factors or other signals?

Answer 12

Cofilin

Question 13

Describe the activation of actin nucleation.

Answer 13

Rac1, a Rho GTPase, is activated/PIP2 -> activates WAVE complex (a type of WASP -> Wave complex uses molecules Arp2/3 to generate a branched actin network.

Question 14

What protects the + end of actin filaments?

Answer 14

Formin family proteins

Question 15

What are integrins composed of?

Answer 15

Heterodimers: alpha and ebta subunits

Question 16

What are the adhesion sites composed of?

Answer 16

Fibronectin in the ECM binds the extracellular portions of integrins. These points serve as traction points for contractile forces.

Question 17

What do adhesion points do (other than adhere)?

Answer 17

Regulate Rho GTPases to control polymerization and organization of actin!

Question 18

How does the trailing edge detach?

Answer 18

1. Rho A, a Rho GTPase, inhibits Rac1 to prevent lamellipodia formation and actomyosin contractility.
2. Microtubule-induced adhesion disassembly.
3. Integrin endocytosis
4. proteolytic cleavage of linker proteins.

Question 19

How does the cell body move?

Answer 19

Molecular clutching, a process that integrates adhesion, retrograde flow, and actin polymerization.

Question 20

What is non-muscle myosin II (NMII)?

Answer 20

A motor protein/ATPase that moves along actin filaments towards the PLUS end (actin filaments provide the track, myosin motor, and AT the energy). This is retrograde flow(??)

Question 21

Describe the structure of NMII.

Answer 21

Globular head (binds actin and ATP)

Light chain linkers (ELC + RLC)

Helical heavy chain

Question 22

What happens when the molecular clutch is disengaged?

Answer 22

Actin is not anchored to the substratum and actin polymerization is counterbalanced by retrograde flow: no movement!

Question 23

What happens when the molecular clutch is engaged?

Answer 23

Actin is coupled to ECM and retrograde flow is impeded b the ECM. New actin polymerization exceeds retrograde flow and the cell moves forward.

Question 24

The ____ chain of the microtubule is the fastest growing.

Answer 24

Beta

Question 25

Can both ends of a microtubule both grow and depolymerize?

Answer 25

Yes

Question 26

In microtubules, the ____ end grows fastest.

Answer 26

+

Question 27

What is the function of gamma tubulin?

Answer 27

Functions as a template for the correct assembly of microtubules

Question 28

What stabilizes the end of of microtubules?

Answer 28

Capping proteins

Question 29

What are MAPS

Answer 29

Microtubuels-associated proteins can stabilize/destabilize/regulate, etc.

Question 30

What does taxol do?

Answer 30

Stabilize microtubules. Used to treat breast cancer, lung cancer, ovarian cancer, Kaposi's sarcoma.

Question 31

What drugs prevent microtubule polymerization?

Answer 31

Colchicine and Vinblastine

Question 32

What does Colchicine treat?

Answer 32

Gout | Familial Mediterranean Fever

Question 33

What does Vinblastine treat?

Answer 33

Testicular and breast caners Lymphomas Kaposi's sarcoma

Question 34

What is the final intermediate filament assembly?

Answer 34

Eight tetramers twisted into a rope-like structure.

Question 35

What are the 3 types of actin monomer subunits?

Answer 35

Alpha Beta Gamma

Question 36

One actin subunit is made of ____ type of actin.

Answer 36

One

Question 37

One strand of actin is amde of ____ actin subunits.

Answer 37

2

Question 38

What types of messengers cause actin filaments to reorganize and move?

Answer 38

Growth factors (e.g. PDGF, EGF, VEGF) Amino acids Second messengers (e.g. Ca2+) Formylated peptides

Question 39

Detachment of the lagging edge is regulated by ____.

Answer 39

Rho A (also a GTPase)

Question 40

Each step of NMII corresponds with hydrolysis of how many ATP?

Answer 40

One

Question 41

What are the 4 steps of movement in actin-myosin contraction?

Answer 41

1. Actin cytoskeleton coupled to the ECM by interaction of actin-binding proteins with integrins. 2. Actin polymerization at front of cell pushes out membrane: leading edge 3. Actomyosin contraction pulls the rear of the cell forward. 4. The cell moves