PXD052814-1

PXD052814 is an original dataset announced via ProteomeXchange.

Title	Structure and Topography of the Synaptic V-ATPase–Synaptophysin Complex
Description	Synaptic vesicles are organelles with a precisely defined protein and lipid composition, 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 brains. The synaptic vesicle V-ATPase is an ATP-dependent proton pump that establishes the protein gradient across the synaptic vesicle, which in turn drives the uptake of neurotransmitters. Synaptophysin and its paralogs synaptoporin and synaptogyrin belong to a family of abundant synaptic vesicle proteins whose function is still unclear. We performed structural and functional studies of synaptophysin knockout mice, confirming the identity of synaptophysin as an interaction partner with the V-ATPase. Although there is little change in the conformation of the V-ATPase upon interaction with synaptophysin, the presence of synaptophysin in synaptic vesicles profoundly affects the copy number of V-ATPases. This effect on the topography of synaptic vesicles suggests that synaptophysin assists in their biogenesis. In support of this model, we observed that synaptophysin knockout mice exhibit severe seizure susceptibility, suggesting an imbalance of neurotransmitter release as a physiological consequence of the absence of synaptophysin.
HostingRepository	iProX
AnnounceDate	2024-06-04
AnnouncementXML	Submission_2024-06-03_22:34:30.312.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xiaotao Shen
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-03 22:34:01	ID requested
⏵ 1	2024-06-03 22:34:30	announced

Dataset with its publication pending

submitter keyword: V-ATPase

Axel T. Brunger
contact affiliation	Stanford University
contact email	brunger@stanford.edu
lab head
Xiaotao Shen
contact affiliation	Nanyang Technological University Singapore
contact email	xiaotao.shen@outlook.com
dataset submitter

iProX dataset URI