Lewin - Neuron death, growth, and neurotrophins Flashcards
What model system was used to study naturally occurring cell death in the dorsal root ganglia (DRG)?
A. male mice
B. female mice
C. chick embryo
D. drosophila
C. chick embryo
What was found via chick embryos regarding cell death and the DRG?
- The amount of target tissue influences neuron survival
- there was less cell death in ganglia that are innervating limbs
What is the neurotrophin hypothesis?
- theres a factor that neurons must take up to survive
- there is a limiting amount of this factor –> some will live, some will die
- match innervating cells to size of the target tissue
- the number of growth factors produced by the cell will determine if it lives or dies
What is Nerve Growth Factor (NGF) and how was it discovered?
- a target-derived soluble factor that can support neuron survival
- implanted tumor cells into the chorion allantoic membrane - compared when tumor cells were placed in embryo (only simulated cell growth in side it was implanted) or directly in the membrane (stimulated cell growth everywhere)
NGF was determined to be some kind of protein. What was used to better understand the nature of this factor?
- snake venom was used to exclude that the factor was nucleic acid (snake venom digests nucleic acid)
- can also use mouse saliva to purify the factor
Neurons can survive without NGF.
A. true
B. false
B. false
Neurons can survive in very low concentrations of NGF, but can’t survive without it
What of the following are true about NGF? (more than one may be true)
A. it is a dimer
B. active form is 15kD Beta-NGF dimer
C. NGF is synthesized as pro NGF
D. NGF serves as a survival factor for a large proportion of peripheral neurons
B. active form is 15kD Beta-NGF dimer
C. NGF is synthesized as pro NGF
D. NGF serves as a survival factor for a large proportion of peripheral neurons
NGF is the only growth factor.
A. true
B. false
B. false
there are 4: NGF, BDNF, NT-3, NT-4
What is TrkA?
- a membrane protein which, when comes together w another TrkA subunit, becomes active an phosphorylates itself
- is a receptor for NGF anf NT3
- has a high affinity (doesn’t need a high concentration)
What is P75?
- a protein that can bind to all GFs, but has a low affinity (requires a high concentration)
- with NGF –> is a survival enhancer
- with proNGF –> promotes cell death
What receptor does BDNF bind to?
TrkB only
What receptor does NT3 bind to?
Trk A,B,C, but has a high affinity to TrkC
What is the interaction between Neurotrophin and Trk receptor?
- when Trk binds to the ligand it dimerises and the receptor can auto-phosphorylate
- these phosphate residues make the proteins recognizable –> signal cascade of activation
- each receptor has a different combination of phosphate residues –> allows for specificity and selectivity
What receptors are involved in cell survival?
A. TrkA
B. TrkB
C. TrkC
D. P75
A. TrkA
B. TrkB
C. TrkC
What receptors are involved in cell death?
A. TrkA
B. TrkB
C. TrkC
D. P75
D. P75