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Activity-dependent synthesis of Emerin gates neuronal plasticity via proteostasis regulation

ABSTRACT: Neurons dynamically regulate their proteome in response to sensory input, a key process underlying experience-dependent structural and functional plasticity. Here, we characterized the visual experience-dependent nascent proteome within a brief, defined time window using an optimized metabolic labeling approach. Visual experience induces cell type-specific and age-dependent alterations in the nascent proteome and recruits proteostasis-related processes. We identified Emerin as the top activity-induced candidate plasticity protein and demonstrated that its activity-induced synthesis is transcription-independent. In contrast to its well-studied nuclear localization and function in myocytes, activity-induced neuronal Emerin is abundant in the ER and broadly inhibits protein synthesis, including synaptic proteins. Downregulating Emerin increases synaptic density, however, it shifts dendritic spines from predominantly mushroom morphology to filopodia, leading to decreased network connectivity, visual responses and visual information processing. Our findings support a visual experience-dependent feed-forward role for Emerin in gating neuronal plasticity through negative regulation of translation.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Hollis T. Cline

PROVIDER: MSV000094390 | MassIVE | Sat Mar 23 15:39:00 GMT 2024

SECONDARY ACCESSION(S): PXD050926

REPOSITORIES: MassIVE

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