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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Publications

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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Project description:Steady-state RNA levels are a result of RNA synthesis and degradation. The importance of transcription-factor mediated induction or repression of mRNA synthesis is well established, but the role and mechanisms of RNA degradation are less well understood. We globally evaluated the RNA decay rates in proliferating and differentiated mouse myoblasts on whole-genome Affymetrix exon arrays, allowing for the assessment of directionality of RNA degradation and the detection of splice variant-specific differences in RNA decay rates. We found large differences in decay rates. mRNAs coding for proteins involved in signal transduction and transcriptional regulation have shortest half lives, whereas mRNAs coding for DNA replication enzymes and muscle contraction proteins are among the most stable. Many genes differentially expressed between proliferating and differentiated myoblasts demonstrate major differences in RNA decay rates. Quantitative PCR experiments confirmed the higher stability of transcripts with increased expression levels. RNA degradation has no apparent preferential directionality. RNA degradation appears to affect the ratio of different splice variants. For example, Itga7 isoforms with higher abundance in differentiated than in proliferating cells are more stable in differentiated cells, despite the sharing of a common 3’ untranslated region. Thus, where it was previously thought that the abundance of different splice isoforms was mainly controlled by tissue-specific splicing factors, we now demonstrate that isoforms may be produced at comparable levels but degraded with different efficiencies, depending on the differentiation status of the cells. Our results indicate that control of RNA degradation rates contributes significantly to the differentiation stage-dependent differences in abundance of transcripts and splice variants. Keywords: total RNA expression profiling; cultured cells We analyzed proliferating C2C12 cells and C2C12 cells differentiated into myotubes by serum starvation (8 days after induction of differentiation). We analyzed 7 time points after addition of actionmycin D (0, 10, 20, 30, 60, 150, 480 minutes). There were two biological replicates per condition.

Dataset Information

Dependence of Synaptic Protein Degradation on Proteasomal Function

Publications

The effects of proteasomal inhibition on synaptic proteostasis.

Similar Datasets

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