L18 - Regulating cell migration

Question 1

what does cell migration rely on

Answer 1

cytokeltal rearrangment –> actin cytoskeleton

Question 2

role of the Arp2/3 complex in migrarting cells

Answer 2

nucleates new actin branches from exsiting filaments

Question 3

what are VCA domains in terms of cell migration

Answer 3

domains in NPFs (nucleation-promoting factors)

V: binds actin monomers
C: central
A: binds Arp2/3

= brings Arp2/3 AND actin monoers together to initiate branching

Question 4

describe the steps in regulation of actin polymerisation

Answer 4

1. Arp2/3 complex binds to SIDE of exisiting actin filament
2. nucleates new filament at 70° angle

= creates branched actin network

3. Arp2/3 activation requires help from NFPs (nucleation-promoting factors)
   - WASP
   - WAVE

= NFPs contain VCA domains

4. VCA domain brings Arp2/3 + actin together to initate branching

= rapid,dense formation of actin filaments that push membrane forward in cell migration

Question 5

what is Rac and its role in cell migration

Answer 5

small GTPase - Rho family - molecular switch

= actiuvates WAVE –> essential for lamelliopodia formation

Question 6

describe Racs role in cell migration/actin polymerisation/ lammeliopodia formation

Answer 6

1. Active Rac-GTP binds to WAVE regulatory complex

= activates WAVE revealing VCA domain

2. VCA donmain binds + activates Arp2/3

= branched actin polymerisation

= Rac -> WAVE -> VCA -> Arp2/3 -> branched actin polymerisation -> membrane protrusion

Question 7

roles of Cofilin and Profilin as ascessory proteins in cell migration

Answer 7

Cofillin = severs off actin filaments –> recycles monomers

Profilin = loads ATP-actin monomers onto growing filaments

= involved in thetreadmilling of growing actin filaments

Question 8

describe what treadmilling is

Answer 8

G-actin added to + end

actin lost from minus end

= even tho filament length remains constant it rapildy grows in directional manner

Question 9

what is CDC42 and what does it cause instead of normal branched actin networks

Answer 9

CDC42 is a Rho family GTPase –> like Rac

actiavtes N-WASP -> a nucleation promoting factor
- like WAVE

N-WASP activates Arp2/3 but in a way that promoyes PARRALEL bundles

= forms filopodia NOT lammeliopodia

Question 10

compare filopodia and lamelliopodia

Answer 10

Filopodia:
- thin,spike like pojection
- parralel + tight actin bundles
- CDC42 -> N-WASP -> Arp2/3
- sneses environment/probes ahead

Lammelliopodia:
- broad sheet-like protrusions
- branched actin networks
- Rac -> WAVE -> Arp2/3
- pushes mmebrane forwards in cell migration