Activity-dependent synthesis of Emerin gates neuronal plasticity by regulating proteostasis

Summary: Neurons dynamically regulate their proteome in response to sensory input, a key process underlying experience-dependent plasticity. We characterized the visual experience-dependent nascent proteome in mice within a brief, defined time window after stimulation using an optimized metabolic la...

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Bibliographic Details
Main Authors: Yi Xie, Ruoxi Wang, Daniel B. McClatchy, Yuanhui Ma, Jolene Diedrich, Manuel Sanchez-Alavez, Michael Petrascheck, John R. Yates, III, Hollis T. Cline
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124725002104
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Summary:Summary: Neurons dynamically regulate their proteome in response to sensory input, a key process underlying experience-dependent plasticity. We characterized the visual experience-dependent nascent proteome in mice within a brief, defined time window after stimulation using an optimized metabolic labeling approach. Visual experience induced cell-type-specific and age-dependent alterations in the nascent proteome, including proteostasis-related proteins. Emerin is the top activity-induced candidate plasticity protein. Activity-induced neuronal Emerin synthesis is rapid and transcription independent. Emerin broadly inhibits protein synthesis, decreasing translation regulators and synaptic proteins. Decreasing Emerin shifted the dendritic spine population from a predominantly mushroom morphology to filopodia and decreased network connectivity. Blocking visual experience-induced Emerin reduced visually evoked electrophysiological responses and impaired behaviorally assessed visual information processing. Our findings support a proteostatic model in which visual experience-induced Emerin provides a feedforward block on further protein synthesis, refining temporal control of activity-induced plasticity proteins and optimizing visual system function.
ISSN:2211-1247