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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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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author Yi Xie
Ruoxi Wang
Daniel B. McClatchy
Yuanhui Ma
Jolene Diedrich
Manuel Sanchez-Alavez
Michael Petrascheck
John R. Yates, III
Hollis T. Cline
author_facet Yi Xie
Ruoxi Wang
Daniel B. McClatchy
Yuanhui Ma
Jolene Diedrich
Manuel Sanchez-Alavez
Michael Petrascheck
John R. Yates, III
Hollis T. Cline
author_sort Yi Xie
collection DOAJ
description 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.
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issn 2211-1247
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series Cell Reports
spelling doaj-art-8964dc4363bd45ee96f0dedda8740bf02025-08-20T03:08:37ZengElsevierCell Reports2211-12472025-04-0144411543910.1016/j.celrep.2025.115439Activity-dependent synthesis of Emerin gates neuronal plasticity by regulating proteostasisYi Xie0Ruoxi Wang1Daniel B. McClatchy2Yuanhui Ma3Jolene Diedrich4Manuel Sanchez-Alavez5Michael Petrascheck6John R. Yates, III7Hollis T. Cline8Department of Neuroscience and Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Skaggs Graduate Program, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Neuroscience and Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Molecular and Cellular Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Molecular and Cellular Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Neuroscience and Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124725002104CP: NeuroscienceCP: Molecular biology
spellingShingle Yi Xie
Ruoxi Wang
Daniel B. McClatchy
Yuanhui Ma
Jolene Diedrich
Manuel Sanchez-Alavez
Michael Petrascheck
John R. Yates, III
Hollis T. Cline
Activity-dependent synthesis of Emerin gates neuronal plasticity by regulating proteostasis
Cell Reports
CP: Neuroscience
CP: Molecular biology
title Activity-dependent synthesis of Emerin gates neuronal plasticity by regulating proteostasis
title_full Activity-dependent synthesis of Emerin gates neuronal plasticity by regulating proteostasis
title_fullStr Activity-dependent synthesis of Emerin gates neuronal plasticity by regulating proteostasis
title_full_unstemmed Activity-dependent synthesis of Emerin gates neuronal plasticity by regulating proteostasis
title_short Activity-dependent synthesis of Emerin gates neuronal plasticity by regulating proteostasis
title_sort activity dependent synthesis of emerin gates neuronal plasticity by regulating proteostasis
topic CP: Neuroscience
CP: Molecular biology
url http://www.sciencedirect.com/science/article/pii/S2211124725002104
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