biostudies-literatureWang CNIMH NIH HHSNCI NIH HHSNIGMS NIH HHS899-904https://www.ebi.ac.uk/biostudies/studies/S-EPMC11269182biostudies-literatureUnknown631(8022)Synaptic vesicles are organelles with a precisely defined protein and lipid composition^1,2, yet the molecular mechanisms for the biogenesis of synaptic vesicles are mainly unknown. Here we discovered a well-defined interface between the synaptic vesicle V-ATPase and synaptophysin by in situ cryo-electron tomography and single-particle cryo-electron microscopy of functional synaptic vesicles isolated from mouse brains³. The synaptic vesicle V-ATPase is an ATP-dependent proton pump that establishes the proton gradient across the synaptic vesicle, which in turn drives the uptake of neurotransmitters^4,5. Synaptophysin⁶ and its paralogues synaptoporin⁷ and synaptogyrin⁸ belong to a family of abundant synaptic vesicle proteins whoNatureStructure and topography of the synaptic V-ATPase-synaptophysin complex.PMC11269182R01 GM114496P30 CA124435T32 GM065103R01 MH063105Jiang LStowell MHBYang KEsquivies LJian RWang CGuo QHampton LBrunger ATLeitz JAdams DJJiang WBasta THeld RGWang XBaumeister WShen XfalseStructure and topography of the synaptic V-ATPase-synaptophysin complex.Synaptic vesicles are organelles with a precisely defined protein and lipid composition^1,2, yet the molecular mechanisms for the biogenesis of synaptic vesicles are mainly unknown. Here we discovered a well-defined interface between the synaptic vesicle V-ATPase and synaptophysin by in situ cryo-electron tomography and single-particle cryo-electron microscopy of functional synaptic vesicles isolated from mouse brains³. The synaptic vesicle V-ATPase is an ATP-dependent proton pump that establishes the proton gradient across the synaptic vesicle, which in turn drives the uptake of neurotransmitters^4,5. Synaptophysin⁶ and its paralogues synaptoporin⁷ and synaptogyrin⁸ belong to a family of abundant synaptic vesicle proteins who2024-01-01T00:00:00Z2024 Jul2026-04-29T23:57:47.879Z2025-04-19T13:09:52.363ZS-EPMC112691823883873710.1038/s41586-024-07610-x