Neurotrophic Factors Flashcards
what are the three structural compenents of a neuron?
soma
dendrites
axon
what are the two transport proteins found in the axon and dendrites and which direction do they work in?
kinesin- anterograde (soma to terminal)
dynein-retrograde (terminal to soma)
what are the three stages of basic extracellular signalling?
reception
transduction
response
describe reception stage of signalling
ligand binds extracellular
changes are intracellular
activates many cellular responses
describe the transduction stage of signalling
signalling cascade of intracellular proteins
what is the relationship between extracellular cues and neuronal survival?
cues promote survival
what are three ways extracellular cues can promote cell survival?
synaptic transmission (establishment of correct connections that lead to electric signals promoting survival) interaction with ECM (survival cues from binfing of neurons to ECM compeonents) extracellular growth factors (neurotrophic factors or neurotrophin)
what are the two ECM components that promote cell survival upon binding to neurons
integrins and laminins
what did Victor Hamburger discover in 1934?
target field regulates neuronal number
suggested that: cue from limb bud causes differentiation of neurons
what happens in absence of limb bud?
less neurons
what did Rita Levi-Montalcini propose in 1942 and 1949?
limb bud factors promote survival- explains hamburgers experiment as when limb bud removed, cell survival factors removed
in 1949, repeated experiment and results supported her theory
what is the neurotrophic factors hypothesis?
once developing neuron has grown its process to target, it competes with other developing neurons of same type for a liimited supply of neurotrophic factors
what does the neurotrophic factors hypothesis imply?
neutrophils are diffusible molecules and not enough neutrophils are made to keeo every neuron alive - limited supply
what are the three summarised stages of neurotrophic factors?
target field release limited supply of diffusible molecules
innervating neurons compete for extracellular signals
those that get enough live, the rest die
what was discovered in 1960?
nerve growth factor
what are four main members of NGF family?
NGF= nerve growth factor
BDNF- brain derived neurotrophic factor
NT3- neurotrophin 3
NT4/5- neurotrophin 4/5
what are four other strains of neurotrophic factors?
GDNF
neurotrophic cytokines
peptide hormones
steroid hormones
what is the purpose of NGF family of neutrophins?
bind to series of transmembrane tyrosine kinas receptors and P75- so they are simply extracellular signals
what are the two types of receptors NGF binds to?
trk and p75
describe NGF binding to Trk receptors (3)
bind with high affinity
binds to trkA
initiates three major signalling pathways
what are the three signalling pathways intiated upon NGF binding to TrkA?
p13k- survival
ras-outgrowth differentiation
plc7-outgrowth synaptic plasticity
describe nGF binding to p75?
binds with low affinity
two pathways are activated- Nfkb and JNK
what trk receptor type do each of the NGF family bind to?
NGF- trkA
NT4/5- trkB
NT3- TrkC
what are the 4 stages of p13 kinase pathway
adapter proteins
p13 kinase
akt kinase
–> cell survival
what are the 4 stages of ras pathway?
GEF Ras kinases MAP kinase --> neurite outgrowht and neuronal differentiation
what are the 3 stages of PLC pathway?
PLC
ip3 or DAG
ca2+ release from ER or PKC
–> neurite outgrowth and differentiation
how are neurotrophins transported around neuron?
retrogradely transported to soma and remove unwanted proteins from nerve terminal for recycling
describe NGF and Nt3 binding to TrkA
NGF complexes are endocytosed and transferred to soma for reterograde transpoer - promotes cell survival via p13k and differentiation via MapK
NT3 complexes signal at the cell surfave and this is local signalling which promotes aonal growth via mapk
describe p75 neutrophin receptor
on own mediates cel death via jnk pathway
when linked by arms to trk it mediates cell sruvival via nfkb
