Regulation of Actin Polymerisation Flashcards
What are the advantages of capping protein?
- Limits length of growing branches so filaments are more effective
- Means actin polymerisation can be favoured at the plasma membrane where Arp 2/3 is activated
What family of proteins are nucleation promoting factors in?
WASp
Give two examples of nucleation promoting factors?
WASP and WAVE
How is WASP inhibited?
Intrinstically inactive due to autoinhibition by CRIB domain which binds to the VCA domain
How is WASP activated?
By Cdc42 which binds to CRIB and releases the VCA domain to bind Arp2/3 complex
How is WAVE activated?
Rac1 binds to Nap/Pir and releases them from WAVE which becomes activated and released so VCA domain can activate Arp2/3
What do GEFs do?
Exchange GDP on inactive GTPase for GTP thus activating them
What is the advantage of having more GEFs and GAPs than GTPases?
- Not all cells produce all GEFs and GAPs
- Allows for regulation to be fine tuned
What is a GAP?
GTPase activating protien
What is the effect of GAPs?
They help promote hydrolysis of GTP to GDP thus inactivating the GTPase
The more actin stress fibres the more slow or fast cell movement?
Slow
What is the MTOC?
Microtubule organising centre
Where is the MTOC found?
Just ahead of the nucleus
What is the role of Cdc42 in cell polarisation?
Migrating cell polarised where Cdc42 is activated and stabilises microtubules
How does Cdc42 stabilise microtubules?
- Cdc42 is associated with IQCAP which binds to CLIP170
- CLIP170 is found at the edge of microtubules and stabilises them
What does downstream signalling of Rho control?
Stress fibres
How does mDia regulate actin polymerisation?
- Associates with growing ends of actin filaments and opens them up
- This allows the actin monomer to bind
- This bind, close, open is repeated
What does mDia do?
Regulates actin polymerisation
What happens to lamellipodia in WAVE knockout mice with constitutively active Rac1?
Lamellipodia are not made
What does inhibition of Rac1 do?
- Prevents lamellipodium formation and inhibits cell migration
Can cells still move in the abscence of Cdc42?
Yes
What happens to cells with RhoA inhibited?
They exhibit long tails incapable of retraction and detachment
What do focal adhesions contain?
Transmembrane Integrins
What happens to focal adhesions during cell movement?
- Focal complexes form at base of lamellipodia
- Complexes remain stationary wrt substrate and new complexes form
- Focal complexes move to rear or Focal complexes are turned over
What is the role of transmembrane integrins in focal adhesions?
- Extracellular domains bind matrix
- Intracellular domains link to actin cytoskeleton
