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

Cell Rep. 2025 Apr 22;44(4):115439. doi: 10.1016/j.celrep.2025.115439. Epub 2025 Apr 9.

Abstract

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.

Keywords: CP: Molecular biology; CP: Neuroscience; Emerin; cell-type-specific proteomics; metabolic protein labeling; protein synthesis; proteostasis; sensory experience-dependent plasticity; synaptic plasticity; visual depth perception; visual response.

MeSH terms

  • Animals
  • Dendritic Spines / metabolism
  • Male
  • Membrane Proteins* / biosynthesis
  • Membrane Proteins* / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Neuronal Plasticity* / physiology
  • Neurons* / metabolism
  • Protein Biosynthesis
  • Proteome / metabolism
  • Proteostasis*

Substances

  • Proteome
  • Membrane Proteins