Dataset Information

Dependence of Synaptic Protein Degradation on Proteasomal Function

ABSTRACT: Synaptic function crucially depends on uninterrupted synthesis and degradation of synaptic proteins. While much has been learned on synaptic protein synthesis, little is known on the routes by which synaptic proteins are degraded. Here we systematically studied how inhibition of the ubiquitin-proteasomal system (UPS) affects the degradation rates of thousands of neuronal and synaptic proteins. We identified a number of proteins, including several proteins related to glutamate receptor trafficking, whose degradation rates were significantly slowed by UPS inhibition. Unexpectedly, however, degradation rates of most synaptic proteins were not significantly affected. Interestingly, many of the differential effects of UPS inhibition were readily explained by a quantitative framework that considered known metabolic turnover rates for the same proteins. In contrast to the limited effects on protein degradation, UPS inhibition profoundly and preferentially suppressed the synthesis of a large number of synaptic proteins. Our findings point to the importance of the UPS in the degradation of certain synaptic proteins, yet indicate that under basal conditions most synaptic proteins might be degraded through alternative pathways.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Brain

SUBMITTER: Tamar Ziv

LAB HEAD: Noam Ziv

PROVIDER: PXD004813 | Pride | 2018-10-26

REPOSITORIES: Pride

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The effects of proteasomal inhibition on synaptic proteostasis.

Hakim Vicky V Cohen Laurie D LD Zuchman Rina R Ziv Tamar T Ziv Noam E NE

The EMBO journal 20160909 20

Synaptic function crucially depends on uninterrupted synthesis and degradation of synaptic proteins. While much has been learned on synaptic protein synthesis, little is known on the routes by which synaptic proteins are degraded. Here we systematically studied how inhibition of the ubiquitin-proteasome system (UPS) affects the degradation rates of thousands of neuronal and synaptic proteins. We identified a group of proteins, including several proteins related to glutamate receptor trafficking, ...[more]

PMID: 27613546

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