Trophic factors and neuronal survival 2 Flashcards
Where on a neuron/neurite does NGF exert its function?
At the tip of a
What does NGF not need to be in contact with for neurites to survive?
The cell body/soma
What if NGF is removed from a culture that previously had it?
Neurites regress
WHat happens to neurite survival if NGF is removed from the soma but kept by the neurites?
Neurites remain
What is the receptor type for NGF?
TRK (tyrosine receptor kinase)
How many pathways can the TRK trigger after NGF binding?
at least 3
What three pathways are triggered by NGF binding to an RTK?
PI3 kinase, ras, PLC
Role of the PI3 kinase pathway?
Promotes cell survival
Role of the ras pathway?
Neurite outgrowth and neuronal differentiation
What does binding of a ligand at a TRK receptor cause?
Phosphorylation of tyrosines to cause phosphotyrosine
ras pathway general idea?
signalling cascade that triggers phosphorylation of ERK, forming phosphoERK
What can phosphoERK do?
Impact on the nucleus–> can affect downstream TFs
Can modify local proteins–> local effect
How does NGF binding to TRK cause cell survival signals (that require the nucleus(cell body))?
NGF-TrkA complex is internalised by the cell, and transported to the cell body/nucleus
How is the NGS-TrkA complex trafficked to the cell body?
In a vesicle (which maintain the active signalling process) along microtubules using dynein motors
Example of a TF activated by the NGF-TrkA complex?
CREB
Does NGF have a widespread effect in the CNS?
No
What was the second neurotrophin to be identified?
BDNF (brain derived neurotrophic factor)
What are important survival factors?
BDNF, NT3 and NT4/5
