The Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, United States; Department of Neuroscience, The Scripps Research Institute, La Jolla, United States; Kellogg School of Science and Technology, The Scripps Research Institute, La Jolla, United States
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States
Lucio Schiapparelli
The Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, United States; Department of Neuroscience, The Scripps Research Institute, La Jolla, United States
Wanhua Shen
The Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, United States; Department of Neuroscience, The Scripps Research Institute, La Jolla, United States; Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China
John R Yates III
Department of Neuroscience, The Scripps Research Institute, La Jolla, United States; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States
The Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, United States; Department of Neuroscience, The Scripps Research Institute, La Jolla, United States; Kellogg School of Science and Technology, The Scripps Research Institute, La Jolla, United States; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, United States
Experience-dependent synaptic plasticity refines brain circuits during development. To identify novel protein synthesis-dependent mechanisms contributing to experience-dependent 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 three 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.
