small GTPases Flashcards
B tubulin is a
GTPase
alpha tubular is not a
GTPase
draw the Btubulun.GTP Btubulin.GDP exchange
what does it drive
Btubulun.GTP
straight filament
Btubulun.GDP
curved protofilament, due to GTP hydrolysis changing subunit conformation, weakens bonds in polymer
what is a GTP cap
adding GTP tubular at the + end which stabilises the protofilament, GDP is unstable
+ end
Btubulin bound to GTP which is more dynamic
loss of GTP cap =
release of tubular –>catastrophic shrinkage
most formins are activated by which GTPase
Rho-gtpase
nucleation of formins
- FH1 and FH2 domains, work like swing arms, sequential working as a dimer with each FH adding an actin monomer
one of the FH monomers adds an actin the other is for
regulagulation proteins such as profilin
actin filaments are nucleated from
the plus end - straight filaments = forming
branched - arp 2/3 complex
thymosin and profilin
compete to bind G actin
- profilin - favours ATP exchange on G actin - pro polymerisation
- thymosin - sequesters actin away from filament - anti-polymerisation
how do GPRCs transduce signals
they use an intermediate GTPase - a large GTPase and then a small gtpase
examples of small GTPases actions
- initiation and elongation
- SRP/SR family
- tubular and cytoskeleton motor
- small monomeric GTPase - Ras superfamily and Rho,Rac and Cdc42 rho gtpase
GAP
GTPase activating protein
increases rate of GTP to GDP bound (inactivating GTPase)
GEF
GTP/GEF exchange factor - activate the exchange
GDI
GDI dissosciation inhibitor - decrease exchange of GTP for GDP
Rho family and what do they do
Rho, Rac and cdc42
relay signals from surface receptors to cytoskeleton and elsewhere
central regulator of cell polarity
cdc42
once activates small GTPase activates target via
molecular switches - or directly small GTPase(2) or through a kinase
localised Cdc42 activation by siganl
recruitment effectors…
- microtubule cytoskeleton
- actin cytoskeleton
- membrane trafficking
- cell contacts
cdc42 in golgi orientation and polarised actin cytoskeleton
cdc42 - WASP - ARP2/3 - actin
cdc42 in centrosome and polarised MTs
cdc42 - PAK - stathmin - MTs
cdc42 in polarised secretion
cdc42 - par cplx - scribble cplx - membrane trafficking - polarised secretion
alternative cdc42 in MTs
cdc42 - parcplx - GSK3/APC - Mts
PAR proteins
- responsible for asymmetric positioning of the mitotic spindle and proteins and RNAs involved in the cells fate distinctions
mutation in PAR proteins
mitotic spindle and PARtitioning defective
Anterior PAR proteins
required to prevent PAR proteins from localising at the anterior and visa versa - POLARISED CELL
LBK1
is a PAR protein in humans
- inactivate, cells are not polarised
- found in the human colon
- mutation - abnormal growth of lining in gut - polyps
Par3 - Par 6 - aPKC complex
epithelial cell polarity
- top/bottom, organelle distribution, membrane lipid composition
apical surface permeable to
H2O, faces the external milieu, SA can be increased
basolateral surface
impermeable, faces internal milieu and blood supply
PAR proteins with crumbs and scribble
- organise cell polarity
- influence each other by phosphorylation, localisation at cell junctions and bind/position small GTPases
tight junction localize
PAR + crumbs
scribble localizes
basolateral junction
Par proteins are
kinases which switch other proteins on/off
scaffolding factors - recruit and interact with other proteins regulating them
cdc42 controls
everything
RhoGTP - focal adhesion
RhoGTP - ROCK- coffin myosin - more stress fibres - focal adhesion
RhoGTP - formin - more stress fibres - focal adhesion
RacGTP - lamellopodia
RacGTP - PAK - filamin myosin - less stress fibres - lamellopodia
RacGTP - WASP - Arp2/3 - branched actin - lamellopodia
cdc42 - filopodia
cdc42 - WASP - Arp 2/3 - branched actin - filopodia
cdc42 - filopodia
cdc42 - WASP - Arp 2/3 - branched actin - filopodia
examples of what CDC42 controls
migrating fibroblast - extending leading edge
cytotoxic T cell - contact with target cell, formation strong contact
epithelial cell - apical basolateral
polarised dividing cell - c.elegans - asymmetric division