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LIFESCI 3B03 Lecture Notes - Microtubule

Life Sciences
Course Code
Margaret Fahnestock

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Axonal Transport
February 10,2014
Neurons Obtain NF by Retrograde Transport from Target Cells from Target Cells, by Paracrine Interactions or by
Making Factors Themselves
Neuron (left) requires NF for survival can get them from a target neuron
Target derived relationship – cell on right secretes NF which is picked u by receptors on terminal axon of cell
and retrogradedly transported to cell body
oNF made by cell body, released by terminal axon; transported down axon in anterograde fashion
oAnterograde - Cell body  terminal
oRetrograde – back to cell body
oNFs going back and forth all the time
Paracrine – trophic factor comes from another cell; any cell in vicinity; usually a glial cell (support cell)
oGlial cells often secrete NF to support neurons
Autocrine – cell supports self; does not need a target neuron or surrounding cells for support
Signaling Endosome
Proteins in pathways cannot be floating in cytoplasm, or will be degraded
Ligand activates receptor at cell surface – some signaling occurs at cells surface
Compartmentalize signaling proteins by signaling endosome
When a receptor is bound by its ligand; Membrane invaginates and forms a vesicle (outside in)
oEg/ Trk bound by NF; Trk internal domain is phosphorylated; can be bound by molecules that organize pathways that serve as bridges
between receptor and pathway
oMolecules like Grb and Shc are bound to Trk once ligand is bund
Outside in vesicle – Trk domain is inside vesicle; what used to be intracellular domain with signaling molecule is now outside of the vesicle
Cargo can attached to dynein, which attaches it to microtubules to be shipped to the nucleus
oIf it meets signaling molecules on the way, can activate them
oMuch of signaling is released at nucleus, where signaling pathways activate transcription factors
oCargo – is the vesicle; signaling endosome
Kinesin and dynein – direction
oDynein – retrograde
oKinesin – anterograde
Dynactin – holds microtubule and cargo together
Neurotrophins are Retrogradedly Transported in Signaling Endosomes
Trk bound by NT Invagination; vesicle is outside-in; phosphorylated binding sites on outside of vesicle  can activate Ras-MAPK pathway, which
phosphorylates dynein as one of its substrates  dynein can bind with cargo and dynactin (microtubule associated protein) in a complex to a cargo 
attach cargo to microtubule
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