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Ubiquitin-proteasome system at the synapse

Citation

Bingol, Baris (2006) Ubiquitin-proteasome system at the synapse. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechETD:etd-05272006-184911

Abstract

Each neuron in the mammalian central nervous system makes up to ten thousand synaptic connections with other neurons yet is able to regulate the strength of individual connections locally. Synaptic enhancement or depression induced at one location on the dendritic arbor does not spread through out the entire neuron. This means neurons must be able to regulate the complement and concentration of the synaptic proteins locally, near synapses. The local concentration of synaptic proteins is influenced by many processes, including protein trafficking, buffering and sequestration, and most directly by protein synthesis and degradation. In recent years, it has been shown that neurons can synthesize proteins locally in their dendrites. These studies have suggested that any cellular process that regulates protein availability could be of importance in regulating synaptic function and plasticity. Indeed, the evidence for the contribution of local protein degradation to the regulation of synaptic function and plasticity has started to emerge in recent years.

Here, we show that synapses have the machinery required to degrade proteins and local protein degradation occurs in the dendrites. Furthermore, we demonstrate the requirement for protein degradation for one of the main cellular correlates of synaptic plasticity, namely the trafficking of glutamate receptors. In turn, we demonstrate how neuronal activity regulates protein degradation at synapses, specifically by mobilizing the enzymatic machinery for protein degradation. These data show that the interplay between protein degradation and synaptic activity functions to sculpt the protein composition of the synapses.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:proteasome; protein degradation; synapse; synaptic plasticity; ubiquitin
Degree Grantor:California Institute of Technology
Division:Biology
Major Option:Biology
Thesis Availability:Restricted to Caltech community only
Research Advisor(s):
  • Schuman, Erin Margaret
Thesis Committee:
  • Zinn, Kai George (chair)
  • Schuman, Erin Margaret
  • Kennedy, Mary B.
  • Deshaies, Raymond Joseph
Defense Date:19 May 2006
Record Number:CaltechETD:etd-05272006-184911
Persistent URL:http://resolver.caltech.edu/CaltechETD:etd-05272006-184911
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:2165
Collection:CaltechTHESIS
Deposited By: Imported from ETD-db
Deposited On:01 Jun 2006
Last Modified:26 Dec 2012 02:47

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