Lecture 6.1 Flashcards
Where does NGF bind and where does it act?
It binds at the synapse and acts on the nucleus with retrograde signalling
What are the components of the axonal skeleton?
Microfilaments within the terminals, intermediate filaments and microtubules
What is spectrin?
Support for the cell membrane of the axonal skeleton
What are the 3 functions of Microtubules?
Axonal transport
Contribute to cell shape
Shuttle organelles inside the cell body
How many filaments make up a microtubule?
13
Where do microtubules originate in the cell?
At the centriole at the negative end
Describe the beta end of a microtubule
+ end, undergoes extension and shortening
Describe the alpha end of a microtubule
- end and is the site of anchoring
Can you have bi directional transport on a microtubule?
yes
To what types of cargo can fast transportation occur?
Only membrane bound cargo ex/ Vesicles or organelles
What 2 proteins carry vesicles along the outside of microtubules and what do they need to function?
Kinesins and Dyneins
ATP
Transport occurs in ….nm hops
5nm (between Dyneins)
Describe the characteristics of Kinesins
They are used in forward movement, need ATP to function, move along a single protofilament of the micrtotubule
Describe the characteristics of Dyneins
For retrograde movement, need ATP
What is the role of the head part of a Kinesin?
To act as the motor by hydrolyzing ATP
Can forward and backward transport occur on one microtubule?
Yes, vesicle do cross without collision
What happens in retrograde transport and give an example of this?
Membrane bound vesicles are returned to the cell body from the distal axon
Retrieval of synaptic vesicle membranes of peptide neurotransmitters
In what direction is slow axonal transport?
Only in forward transport
What proteins use slow axonal transport?
Structural proteins ex/ Neurofilament
Is slow axonal transport efficient?
Nope
Neural circuits are dependent on ……..
Neurotrophin and activity
What is an example of a neurotrophin and what is its receptor?
Nerve growth factor and TrkA
Describe the retrograde signalling of NGF and TrkA
NGF comes into the distal axon by binding to TrkA. NGF forms in the center of a vesicle that is surrounded by TrkA receptors. As the vesicle moves back up the axon i na retrograde fashion, the vesicle is continuously signalling due to active TrkA. The vesicle reaches the nucleus in the cell body and enters the gene expression cycle leading to an increase in signalling for an increase in neurotransmitter production
Describe the 4 Neurotrophin examples and their receptors
NGF-Trk A
BDNF- TrK B
NT3- TrK C
NT4- TrK B
Is TrKA the only receptor when acting with neurotrophins
No, co-receptor is p75, this increases sensitivity
What occurs in the absence of TrK receptors?
Cell death
What are the actions of Neurotrophins in the developing nervous system?
Neuronal differentiation, neuronal survival, neuronal guidance, axonal growth
What are the actions of Neurotrophins in the mature nervous system?
Axonal growth and maintaining normal neuronal function
What occurs with withdrawal of Neurotrophin in mature neurons?
Decreased transmitter production/transmitter release
Retraction of axonal branches
Reduction in cell body size
What are NGF targets?
Nociceptive sensory neurons
Sympathetic ganglia
Cholinergic neurons in basal forebrain
Describe the anatomy of NGF
Two identical 118 amino acid monomers that are back to back
They are bound due to when they come together, each monomer has a TrkA receptor binding site in which the two sites come together
