17 - Regulation of Cell Migration Flashcards
What are Small GTPases?
They are signalling proteins and members of the G-protein family, they have a role in hydrolysing GTP, Some of them include:
- Arf, Ras, Rho Rab
What is Ras?
A small GTPase responsible for cell proliferation, its also one of the largest groups of signalling proteins.
What is Rab?
A small GTPase responsible for endosomal trafficking.
What is Rho?
A small GTPase responsible for migration and the structure if the cells cytoskeleton.
What is Arf?
A small GTPase responsible for membrane budding.
What does GTPase signalling depend on?
The bound nucleotide
What is unique about active Arf6?
It is inhibitory
What controls the shape of the GTPase?
The P-Loop (phosphate binding loop)
What happens when magnesium is removed?
The nucleotide falls off.
what do the switch regions 1 and 2 do?
They along with their interactions help to bind the effectors.
How do we detect an active GTPase?
By effector binding, they are evolved to be matched to the loops so they can detect whether the GTPase is active or inactive.
What are the 2 steps in The catalysis of GTP hydrolysis?
1) The positioning of attacking water-
Which is carried out by catalytic glutamine and hydrolyses the
alpha-beta subunit.
2) Counteracting the negative charge at the phosphates.
What are the active mutants in the catalysis of GTP hydrolysis and what do they do?
- The Q61L mutant which acts as a catalytic mutant.
- The G12V which pushes out the Q61 disturbing the P-loop.
How do the mutants effect hydrolysis?
It reduces it 10-fold.
What is the role of GEFs (guanine nucleotide exchange factors) in the cyclic regulation of GTPases?
- They speed up the transition of GTP to GDP
- They stabilise nucleotide free, magnesium free GTPases.
What is the role of GAPs (GTPase activating proteins)?
They activate the hydrolysis function and so turn off the signalling.
What is the role of GDIs (Guanine nucleotide dissociation inhibitors)?
They bind to GTPase and hold it in the cytosol, then switch it off
What regulates actin based motility?
Rac
What small GTPase is responsible for the contractility in actin based motility?
RhoA
What happens if a growth factor is used to stimulate migration?
The cell will move towards the growth factor.
What structure helps to move the cell towards the growth factor?
Filipodium.
What Small GTPase causes the growth of the filipodium towards the growth factor?
Cdc42
What small GTPase is responsible for the growth of lamellopodia (Protruion) and the formation of new adhesions towards the growth factor?
Rac1
What small GTPase is responsible for the formation of actin stress fibres (contractility) pulling forward the body of the cell?
RhoA
What are the 2 protrusive signals?
Cdc42 and Rac
What is the contractile signal?
RhoA
How do the protrusive and contractile signals work together?
They work against each other, backwards and forwards to get the cell moving forward.
What does migration guidance do for the cell?
Helps them to translocate more efficiently.
