Ubiquitin ligase TRIM3 controls hippocampal plasticity and learning by regulating synaptic γ-actin levels

Joerg Schreiber, Marlene J Végh, Julia Dawitz, Tim Kroon, Maarten Loos, Dorthe Labonté, Ka Wan Li, Pim Van Nierop, Michiel T Van Diepen, Chris I De Zeeuw, Matthias Kneussel, Rhiannon M Meredith, August B Smit, Ronald E Van Kesteren

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Samenvatting

Synaptic plasticity requires remodeling of the actin cytoskeleton. Although two actin isoforms, β- and γ-actin, are expressed in dendritic spines, the specific contribution of γ-actin in the expression of synaptic plasticity is unknown. We show that synaptic γ-actin levels are regulated by the E3 ubiquitin ligase TRIM3. TRIM3 protein and Actg1 transcript are colocalized in messenger ribonucleoprotein granules responsible for the dendritic targeting of messenger RNAs. TRIM3 polyubiquitylates γ-actin, most likely cotranslationally at synaptic sites. Trim3(-/-) mice consequently have increased levels of γ-actin at hippocampal synapses, resulting in higher spine densities, increased long-term potentiation, and enhanced short-term contextual fear memory consolidation. Interestingly, hippocampal deletion of Actg1 caused an increase in long-term fear memory. Collectively, our findings suggest that temporal control of γ-actin levels by TRIM3 is required to regulate the timing of hippocampal plasticity. We propose a model in which TRIM3 regulates synaptic γ-actin turnover and actin filament stability and thus forms a transient inhibitory constraint on the expression of hippocampal synaptic plasticity.

Originele taal-2Engels
Pagina's (van-tot)569-86
Aantal pagina's18
TijdschriftJournal of Cell Biology
Volume211
Nummer van het tijdschrift3
DOI's
StatusGepubliceerd - 09 nov 2015

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