Identifying and Characterizing Novel Mechanisms in the Establishment and Maintenance of Synapses in Drosophila

Simple item page
dc.contributor.advisorPrehoda, Ken
dc.contributor.authorSpinner, Michael
dc.date.accessioned2018-09-06T22:02:30Z
dc.date.issued2018-09-06
dc.description.abstractSynapse development is a stepwise process that requires the recruitment of key synaptic components to active zones, followed by continual maintenance of these structures to maintain connectivity and stability throughout the life of the organisms. Early synapse development requires the recruitment of early scaffolding proteins to establish stable connectivity as well as provide sites of recruitment of other vital synaptic proteins. One of the earliest proteins to be localized to the synapse is the conserved protein Syd-1. Syd-1 proteins contain a Rho GTPase activating protein (GAP)-like domain of unclear significance. Here I show that Drosophila Syd-1 interacts with all six fly Rhos and has GAP activity towards RAC1. I then show that lacks GAP activity localizes normally to presynaptic sites and is sufficient to recruit Nrx-1 but fails to cluster Brp normally and genetically interacts with RAC1 in vivo. I conclude that contrary to previous models, the GAP domain of fly Syd-1 is active and required for presynaptic development. Additionally, I’ve identified a previously uncharacterized protein, Vezl, as being critical for retrograde axonal transport and synaptic maintenance. I found that Vezl required for normal neuronal growth and that vezl loss resulted in decreased neuron size and the formation of swollen neuronal terminals that accumulated membrane markers and axonal transport cargo. I found that vezl mutants specifically retrograde transport of cargo and particularly affected signaling endosomes. The signaling endosomes were unable to initiate retrograde transport in vezl mutants and remained stuck within the distal boutons unable to relay their signaling peptides back to the nucleus. I conclude that Vezl is serving a role in attaching retrograde cargo to dynein and the microtubules specifically at neuron tips so that they can undergo retrograde axonal transport. This dissertation includes previously published and unpublished co-authored material.en_US
dc.description.embargo2020-09-06
dc.identifier.urihttps://hdl.handle.net/1794/23818
dc.language.isoen_US
dc.publisherUniversity of Oregon
dc.rightsAll Rights Reserved.
dc.subjectActive zonesen_US
dc.subjectAxonal transporten_US
dc.subjectNeuromuscular junctionen_US
dc.subjectSyd-1en_US
dc.subjectSynaptogenesisen_US
dc.subjectVezatinen_US
dc.titleIdentifying and Characterizing Novel Mechanisms in the Establishment and Maintenance of Synapses in Drosophila
dc.typeElectronic Thesis or Dissertation
thesis.degree.disciplineDepartment of Chemistry and Biochemistry
thesis.degree.grantorUniversity of Oregon
thesis.degree.leveldoctoral
thesis.degree.namePh.D.

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Spinner_oregon_0171A_12250.pdf
Size:
8.02 MB
Format:
Adobe Portable Document Format
Download

Collections

Theses and Dissertations
Chemistry Theses and Dissertations