Role of the Visual Experience-Dependent Nascent Proteome in Neuronal Plasticity

Abstract

SummaryExperience-dependent synaptic plasticity refines brain circuits during development. To identify novel protein synthesis-dependent mechanisms contributing to experiencedependent plasticity, we conducted a quantitative proteomic screen of the nascent proteome in response to visual experience in Xenopus optic tectum using bio-orthogonal metabolic labeling (BONCAT). We identified 83 differentially synthesized candidate plasticity proteins (CPPs). The CPPs form strongly interconnected networks and are annotated to a variety of biological functions, including RNA splicing, protein translation, and chromatin remodeling. Functional analysis of select CPPs revealed the requirement for eukaryotic initiation factor 3 subunit A (eIF3A), fused in sarcoma (FUS), and ribosomal protein s17 (RPS17) in experience-dependent structural plasticity in tectal neurons and behavioral plasticity in tadpoles. These results demonstrate that the nascent proteome is dynamic in response to visual experience and that de novo synthesis of machinery that regulates RNA splicing and protein translation is required for experience-dependent plasticity.

Cell-Surface Proteomic Profiling in the Fly Brain Uncovers Wiring Regulators

“…Chemical labeling enables enrichment of cell-surface proteins (Nunomura et al, 2005;Wollscheid et al, 2009;Zhang et al, 2003) but does not provide cell type specificity. Alternative technologies for cell-type-specific proteomics, such as bio-orthogonal metabolic labeling (Alvarez-Castelao et al, 2017;Liu et al, 2018) or organelle tagging (Fecher et al, 2019), are not amenable to analysis of cell-surface proteomes specifically.…”

Proteome Turnover in the Spotlight: Approaches, Applications, and Perspectives

“…They usually carry an azido or alkyne functional group and can thus be immobilized on a solid phase using click chemistry and affinity purification. Although initially developed for neurobiological applications ( 95 , 96 , 97 , 98 ), the technique has since been applied to multiple systems, including primary cells ( 99 ), tissue sections ( 98 ), and in vivo in a variety of organisms, including bacteria ( 100 ), archaea ( 101 ), plants ( 102 ), zebrafish ( 97 ), and other higher eukaryotes ( 103 , 104 ). BONCAT can also be used to visualize overall proteome synthesis in cells using fluorescent non-canonical amino acid tagging ( 105 ) or to measure synthesis of target proteins in a spatially resolved manner using a proximity ligation assay ( 106 ).…”

Effect of Electroacupuncture on Pain Perception and Pain-Related Affection: Dissociation or Interaction Based on the Anterior Cingulate Cortex and S1

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