Neurotrophic Factors

Question 1

what are the three structural compenents of a neuron?

Answer 1

soma
dendrites
axon

Question 2

what are the two transport proteins found in the axon and dendrites and which direction do they work in?

Answer 2

kinesin- anterograde (soma to terminal)

dynein-retrograde (terminal to soma)

Question 3

what are the three stages of basic extracellular signalling?

Answer 3

reception
transduction
response

Question 4

describe reception stage of signalling

Answer 4

ligand binds extracellular
changes are intracellular
activates many cellular responses

Question 5

describe the transduction stage of signalling

Answer 5

signalling cascade of intracellular proteins

Question 6

what is the relationship between extracellular cues and neuronal survival?

Answer 6

cues promote survival

Question 7

what are three ways extracellular cues can promote cell survival?

Answer 7

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)

Question 8

what are the two ECM components that promote cell survival upon binding to neurons

Answer 8

integrins and laminins

Question 9

what did Victor Hamburger discover in 1934?

Answer 9

target field regulates neuronal number

suggested that: cue from limb bud causes differentiation of neurons

Question 10

what happens in absence of limb bud?

Answer 10

less neurons

Question 11

what did Rita Levi-Montalcini propose in 1942 and 1949?

Answer 11

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

Question 12

what is the neurotrophic factors hypothesis?

Answer 12

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

Question 13

what does the neurotrophic factors hypothesis imply?

Answer 13

neutrophils are diffusible molecules and not enough neutrophils are made to keeo every neuron alive - limited supply

Question 14

what are the three summarised stages of neurotrophic factors?

Answer 14

target field release limited supply of diffusible molecules
innervating neurons compete for extracellular signals
those that get enough live, the rest die

Question 15

what was discovered in 1960?

Answer 15

nerve growth factor

Question 16

what are four main members of NGF family?

Answer 16

NGF= nerve growth factor
BDNF- brain derived neurotrophic factor
NT3- neurotrophin 3
NT4/5- neurotrophin 4/5

Question 17

what are four other strains of neurotrophic factors?

Answer 17

GDNF
neurotrophic cytokines
peptide hormones
steroid hormones

Question 18

what is the purpose of NGF family of neutrophins?

Answer 18

bind to series of transmembrane tyrosine kinas receptors and P75- so they are simply extracellular signals

Question 19

what are the two types of receptors NGF binds to?

Answer 19

trk and p75

Question 20

describe NGF binding to Trk receptors (3)

Answer 20

bind with high affinity
binds to trkA
initiates three major signalling pathways

Question 21

what are the three signalling pathways intiated upon NGF binding to TrkA?

Answer 21

p13k- survival
ras-outgrowth differentiation
plc7-outgrowth synaptic plasticity

Question 22

describe nGF binding to p75?

Answer 22

binds with low affinity

two pathways are activated- Nfkb and JNK

Question 23

what trk receptor type do each of the NGF family bind to?

Answer 23

NGF- trkA
NT4/5- trkB
NT3- TrkC

Question 24

what are the 4 stages of p13 kinase pathway

Answer 24

adapter proteins
p13 kinase
akt kinase
–> cell survival

Question 25

what are the 4 stages of ras pathway?

Answer 25

GEF
Ras
kinases
MAP kinase
--> neurite outgrowht and neuronal differentiation

Question 26

what are the 3 stages of PLC pathway?

Answer 26

PLC
ip3 or DAG
ca2+ release from ER or PKC
–> neurite outgrowth and differentiation

Question 27

how are neurotrophins transported around neuron?

Answer 27

retrogradely transported to soma and remove unwanted proteins from nerve terminal for recycling

Question 28

describe NGF and Nt3 binding to TrkA

Answer 28

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

Question 29

describe p75 neutrophin receptor

Answer 29

on own mediates cel death via jnk pathway

when linked by arms to trk it mediates cell sruvival via nfkb