Core Concepts
The synaptic vesicle V-ATPase and synaptophysin form a well-defined complex that is crucial for the biogenesis and function of synaptic vesicles, with implications for neurotransmitter release and seizure susceptibility.
Abstract
The content provides insights into the structural and functional relationship between the synaptic vesicle V-ATPase and the protein synaptophysin. Key highlights:
- The V-ATPase is an ATP-dependent proton pump that establishes the protein gradient across the synaptic vesicle, driving the uptake of neurotransmitters.
- Synaptophysin and its paralogs (synaptoporin and synaptogyrin) are abundant synaptic vesicle proteins with unclear functions.
- Using cryo-electron tomography and microscopy, the authors discovered a well-defined interface between the V-ATPase and synaptophysin in functional synaptic vesicles isolated from mouse brains.
- While the conformation of the V-ATPase is largely unaffected by the interaction with synaptophysin, the presence of synaptophysin significantly impacts the copy number of V-ATPases on synaptic vesicles.
- Synaptophysin knockout mice exhibit severe seizure susceptibility, suggesting that the V-ATPase-synaptophysin complex is crucial for the proper biogenesis and function of synaptic vesicles, with implications for neurotransmitter release.
- The study provides structural and functional insights into the role of the V-ATPase-synaptophysin complex in the biogenesis and regulation of synaptic vesicles, which is important for understanding neurotransmission and neurological disorders.
Stats
Synaptic vesicles have a precisely defined protein and lipid composition.
The synaptic vesicle V-ATPase is an ATP-dependent proton pump that establishes the protein gradient across the synaptic vesicle.
Synaptophysin and its paralogs (synaptoporin and synaptogyrin) are abundant synaptic vesicle proteins.
Synaptophysin knockout mice exhibit severe seizure susceptibility.
Quotes
"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."
"We performed structural and functional studies of synaptophysin knockout mice, confirming the identity of synaptophysin as an interaction partner with the V-ATPase."
"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."