Lecture 14: Cytoskeleton Motility + Connective Tissue

Question 1

Cell locomotion process

Answer 1

1. Protrusion of leading edge
2. Adhesion of leading edge, detachment of trailing edge
3. Movement of cell body

Question 2

What triggers protrusion of the leading edge?

Answer 2

f-actin at the leading edge continuously reorganizes in response to extracellular signals (GFs, AAs, 2o messengers, etc.)

Question 3

What role does actin have in protrusion?

Answer 3

Rho-GTP binding factors respond to EC signals (Rac1 at front, Rho A at back) and activate actin nucleation via Arp2/3

Question 4

Arp2/3

Answer 4

Stimulates actin nucleation and enables branching

Question 5

Cofilin

Answer 5

Enzyme that cuts and depolymerizes f-actin toward the “older” (-) end, freeing up more g-actin for further polymerization

Question 6

Formin

Answer 6

Capping protein that prevents further extension of (+) end of f-actin. Regulates movement and direction.

Question 7

How does the leading edge attach/detach from the ECM?

Answer 7

Attachment is mediated by transmembrane integrins, which interact with both the ECM and cytoskeleton. Rho A stimulates detachment at the trailing edge

Question 8

Integrins

Answer 8

αβ dimers that reads EC signals to change IC actin, or reads IC actin changes to remodel the ECM

Question 9

Cell body movement mechanisms

Answer 9

1. Actomyosin contraction
2. Molecular clutching

Question 10

How does actomyosin contraction work?

Answer 10

Non-Muscle Myosin II (NMII) forms an antiparallel bipolar filament dimer that pulls actin filaments across each other

Question 11

How does molecular clutching work?

Answer 11

When the clutch is engaged, transmembrane integrins link to the actin cytoskeleton, anchoring it to the ECM. When disengaged, actin is not anchored and polymerization can’t exert force on the leading edge.

Question 12

How do the molecular clutch and actomyosin contraction coordinate?

Answer 12

1. Actin couples to the ECM via integrins.
2. Actin polymerization pushes the leading edge forward.
3. Actomyosin contraction pulls the rear of the cell forward.
4. Cell moves.