Structure and topography of the synaptic V-ATPase–synaptophysin complex

Chuchu Wang, Wenhong Jiang, Jeremy Leitz, Kailu Yang, Luis Esquivies, Xing Wang, Xiaotao Shen, Richard G. Held, Daniel J. Adams, Tamara Basta, Lucas Hampton, Ruiqi Jian, Lihua Jiang, Michael H. B. Stowell, Wolfgang Baumeister, Qiang Guo () and Axel T. Brunger ()
Additional contact information
Chuchu Wang: Stanford University
Wenhong Jiang: Peking University
Jeremy Leitz: Stanford University
Kailu Yang: Stanford University
Luis Esquivies: Stanford University
Xing Wang: Peking University
Xiaotao Shen: Stanford University
Richard G. Held: Stanford University
Daniel J. Adams: University of Colorado
Tamara Basta: University of Colorado
Lucas Hampton: University of Colorado
Ruiqi Jian: Stanford University
Lihua Jiang: Stanford University
Michael H. B. Stowell: University of Colorado
Wolfgang Baumeister: Max Planck Institute of Biochemistry
Qiang Guo: Peking University
Axel T. Brunger: Stanford University

Nature, 2024, vol. 631, issue 8022, 899-904

Abstract: Abstract Synaptic vesicles are organelles with a precisely defined protein and lipid composition1,2, 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 neurotransmitters4,5. Synaptophysin6 and its paralogues synaptoporin7 and synaptogyrin8 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.

Date: 2024
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-024-07610-x Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:631:y:2024:i:8022:d:10.1038_s41586-024-07610-x

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-024-07610-x

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().