Protein Trafficking Flashcards
(59 cards)
What can polarity be maintained by?
- physical barrier (AIS)
- selective trafficking
- selective retention
- selective degradation
- local translation
What is localised translation?
when certain proteins are synthesised away from the cell body
When does the axon initial segment (AIS) form?
after axon establishment
What does the molecular sieve do?
- prevent free diffusion of selected membrane and cytoplasmic proteins into axons
- regulate the initiation of APs
What does the AIS have a similar molecular organisation to?
node of Ranvier
What is the key difference between the axon hillock and the AIS?
the axon hillock is present in the cell body of the neuron while the AIS is present in the proximal part of the axon
What is the role of the AIS in polarity maintenance?
- serves as a submembrane diffusion barrier that restricts the mobility of plasma membrane components
- acts as an intracellular selective filter for the transport of organelles and molecules through the cytoplasm
What is inter-compartmental transport essential for?
communication and support
Why are proteins and organelles in constant motion?
- synapse formation (from sites of synthesis to sites of function)
- for degradation
- for everyday requirements
In axonal transport, where is the plus and minus end respectively?
- minus = cell body
- plus = extremities
What are kinesins?
plus end motors with 45 genes that take newly synthesised proteins from the cell out to the axon terminal
What is kinesin-13 and 14 respectively?
- 13 = MT depolymerising (catastrophe promoting)
- 14 = minus-end directed
What are the 3 major domains of a kinesin motor?
- tail (cargo binding and auto inhibition mediation)
- stalk (dimerisation domain)
- head (motor domain)
What are the 6 steps of kinesin walking along an MT?
- in solution, both kinesin heads contain tightly bound ADP and move randomly
- when one of the heads (M2) encounters an MT, it binds tightly and releases ADP
- ATP rapidly enters the nucleotide binding site which triggers the neck linker to zipper onto the catalytic core
- this action throws the second head (M1) forward and brings it into contact with the next MT binding site
- the trailing head hydrolyses ATP, releasing phosphate
- the neck linker unzips from the trailing head and the leading head exchanges its nucleotide which allows it to zip to the catalytic core and the cycle repeats
How does the tail of kinesin bind the cargo?
via adapter proteins
Give an example of a cargo that binds directly to the tail domain without the need of adapter proteins
SNAP25
How can kinesin autoinhibition be relieved?
by cargo binding and phosphorylation mechanisms
How do autoinhibited kinesins work?
dual inhibitory mechanisms control kinesin-1, 2 and 3 motors through domains that inhibit MT binding and domains that inhibit processive motility
How can kinesin-1 motors be reactivated after autoinhibition by cargo binding?
the interaction with FEZ1 and JIP1 that releases the restraints of MT binding and processive motility
How can kinesin-7 motors be reactivated after autoinhibition by phosphorylation?
phosphorylation of the inhibitory tail domain by the kinases MPS1 and CDK1-cyclin B, which results in processive motility on MTs
What is the lifecycle of kinesin motors?
- in the absence of cargo, kinesin motors are autoinhibited
- during transport, motor-cargo complexes must navigate MT tracks
- at the destination, cargo release is coupled to inactivation of the motor
What is dynein?
a minus-end motor (only 1 motor, kinesin has 5)
What is dynein made up of?
- 2 heavy chains
- 2 intermediate chains
- 2 light intermediate chains
- 2 light chains
What are the 3 domains of each dynein HC?
- head (motor) domain with ATPase activity
- linker domain where MTs bind, and movement is generated
- tail domain involved in dimerisation and cargo binding
