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Updated: Jun 24, 2025

Visualization of ATP Synthase Dimers in Mitochondria by Electron Cryo-tomography
Published on: September 14, 2014
Structure and topography of the synaptic V-ATPase-synaptophysin complex
Chuchu Wang1,2,3,4,5, Wenhong Jiang6, Jeremy Leitz1,2,3,4,5
1Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA.
Researchers discovered a key interaction between the V-ATPase and synaptophysin in synaptic vesicles. This finding sheds light on synaptic vesicle biogenesis and neurotransmitter release, impacting neurological function.
Area of Science:
- Neuroscience
- Cell Biology
- Structural Biology
Background:
- Synaptic vesicles are crucial for neurotransmission, but their biogenesis mechanisms remain largely unknown.
- The V-ATPase proton pump and synaptophysin are abundant synaptic vesicle proteins with unclear functional roles.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying synaptic vesicle biogenesis.
- To investigate the interaction between the V-ATPase and synaptophysin and its functional consequences.
Main Methods:
- In situ cryo-electron tomography and single-particle cryo-electron microscopy of isolated mouse brain synaptic vesicles.
- Structural and functional studies using synaptophysin-knockout mice.
Main Results:
- A well-defined interface between the synaptic vesicle V-ATPase and synaptophysin was identified.
- Synaptophysin binding to V-ATPase affects V-ATPase copy number on synaptic vesicles, suggesting a role in biogenesis.
- Synaptophysin-knockout mice display severe seizure susceptibility, indicating impaired neurotransmitter release.
Conclusions:
- Synaptophysin plays a critical role in synaptic vesicle biogenesis by modulating V-ATPase incorporation.
- The V-ATPase-synaptophysin interaction is essential for maintaining proper neurotransmitter release and neuronal function.
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