Seminars

January 12 2015

12:30 158 Hershey Hall

Gentry Patrick
Division of Biological Sciences, Section of Neurology University of California, San Diego

Destruction as a means of remodeling: the many roles of ubiquitin at the synapse

Summary

The inherent turnover rate \(half-life, t \) for any given protein is determined by a combination of its synthesis and degradation. Importantly, cell biological signals are capable of altering rates of synthesis, degradation or both. In neurons, this may contribute to the dynamic nature of the overall protein stoichiometry of functionally relevant microdomains such as synapses. Ubiquitination \(also known as ubiquitylation\) has emerged as a functionally relevant post-translational modification of many synaptic proteins. Ubiquitination can promote the targeting of protein substrates to the 26S proteasome and to the lysosome, the major sites of protein degradation in eukaryotic cells. Synaptic plasticity is largely mediated by both morphological and functional modifications to synapses. It is now clear that ubiquitin-dependent protein degradation plays a major role in the development, maintenance and remodeling of synaptic connections in the brain. Over the years, my lab has focused on a central question: How does neuronal activity regulate ubiquitin-dependent synaptic protein degradation. Interestingly, the activity-dependent rules we have uncovered involves not only the regulation substrate ubiquitination \(e.g. regulation of ubiquitin ligases or deubiquitinating enzymes\), but also the activity and trafficking of the 26S proteasome and the availability of free ubiquitin \(e.g. ubiquitin homeostasis\). In this seminar I will discuss our past and recent findings for activity-dependent protein degradation at synapses. A major focus will describe the activity-dependent ubiquitination and trafficking of AMPA-type glutamate receptors and the regulation of the 26S proteasome at synapses.

 

 

 

 

 

 

 

 

 

 

 



 

 

 

 

 

 

 

 

 

 

 

 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



this is idtest: