Molecular organization of central cholinergic synapses

• 成果类型: Article
• 署名作者: Rosenthal, Justin S.; Zhang, Dean; Yin, Jun; Long, Caixia; Yang, George; Li, Yan; Lu, Zhiyuan; Li, Wei-Ping; Yu, Zhiheng; Li, Jiefu; Yuan, Quan
• 署名单位: National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS); Howard Hughes Medical Institute
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11033
• DOI: 10.1073/pnas.2422173122
• 发表日期: 2025-04-29
• 关键词: nicotinic acetylcholine-receptor; neuromuscular-junction formation; nmda receptors; proteomic analysis; in-vivo; drosophila; proteins; plasticity; identification; TRAFFICKING

摘要

Synapses have undergone significant diversification and adaptation, contributing to the complexity of the central nervous system. Understanding their molecular architecture is essential for deciphering the brain's functional evolution. While nicotinic acetylcholine receptors (nAchRs) are widely distributed across metazoan brains, their associated protein networks remain poorly characterized. Using in vivo proximity labeling, we generated proteomic maps of subunit- specific nAchR interactomes in developing and mature Drosophila brains. Our findings reveal a developmental expansion and reconfiguration of the nAchR interactome. Proteome profiling with genetic perturbations showed that removing individual nAchR subunits consistently triggers compensatory shifts in receptor subtypes, highlighting mechanisms of synaptic plasticity. We also identified loss of Sif disrupting their molecular composition and structural integrity. These results provide molecular insights into the development and plasticity of central cholinergic synapses, advancing our understanding of synaptic identity conservation and divergence.