Coordination between translation and degradation regulates inducibility of mGluR-LTD

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Dendritic protein homeostasis is crucial for most forms of long-term synaptic plasticity, and its dysregulation is linked to a wide range of brain disorders. Current models of metabotropic glutamate receptor mediated long-term depression (mGluR-LTD) suggest that rapid, local synthesis of key proteins is necessary for the induction and expression of LTD. Here, we find that mGluR-LTD can be induced in the absence of translation if the proteasome is concurrently inhibited. We report that enhanced proteasomal degradation during the expression of mGluR-LTD depletes dendritic proteins and inhibits subsequent inductions of LTD. Moreover, proteasome inhibition can rescue mGluR-LTD in mice null for the RNA binding protein Sam68, which we show here lack mGluR-dependent translation and LTD. Our study provides mechanistic insights for how changes in dendritic protein abundance regulate mGluR-LTD induction. We propose that Sam68-mediated translation helps to counterbalance degradation, ensuring that protein levels briefly remain above a permissive threshold during LTD induction.

Original languageEnglish (US)
Pages (from-to)1459-1466
Number of pages8
JournalCell Reports
Volume10
Issue number9
DOIs
StatePublished - Mar 10 2015

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Metabotropic Glutamate Receptors
Degradation
Proteasome Endopeptidase Complex
Proteins
Neuronal Plasticity
RNA-Binding Proteins
Brain Diseases
Proteolysis
Plasticity
Brain
Homeostasis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Coordination between translation and degradation regulates inducibility of mGluR-LTD. / Klein, Matthew E.; Castillo, Pablo E.; Jordan, Bryen A.

In: Cell Reports, Vol. 10, No. 9, 10.03.2015, p. 1459-1466.

Research output: Contribution to journalArticle

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