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-Structure paper
タイトル | Structure and topography of the synaptic V-ATPase-synaptophysin complex. |
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ジャーナル・号・ページ | Nature, Vol. 631, Issue 8022, Page 899-904, Year 2024 |
掲載日 | 2024年6月5日 |
![]() | 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 / Axel T Brunger / ![]() ![]() ![]() ![]() |
PubMed 要旨 | 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 ...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 proton gradient across the synaptic vesicle, which in turn drives the uptake of neurotransmitters. Synaptophysin and its paralogues 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. |
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手法 | EM (単粒子) / EM (トモグラフィー) / EM (サブトモグラム平均) |
解像度 | 3.6 - 18.2 Å |
構造データ | EMDB-44839, PDB-9bra: EMDB-44840, PDB-9brq: EMDB-44841, PDB-9brr: EMDB-44842, PDB-9brs: EMDB-44843, PDB-9brt: EMDB-44844, PDB-9bru: EMDB-44845, PDB-9bry: EMDB-44846, PDB-9brz: ![]() EMDB-44847: Tomograms of isolated synaptic vesicles from Syp-/- mouse brain ![]() EMDB-44848: Tomograms of isolated synaptic vesicles from wild-type mouse brain ![]() EMDB-44855: Intact state1 V-ATPase of isolated synaptic vesicles from wild-type mouse brain by subtomogram averaging ![]() EMDB-44856: Intact state2 V-ATPase of isolated synaptic vesicles from wild-type mouse brain by subtomogram averaging ![]() EMDB-44857: Intact state3 V-ATPase of isolated synaptic vesicles from wild-type mouse brain by subtomogram averaging ![]() EMDB-44858: V0-only V-ATPase of isolated synaptic vesicles from wild-type mouse brain by subtomogram averaging |
化合物 | ![]() ChemComp-NAG: ![]() ChemComp-BMA: |
由来 |
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![]() | MEMBRANE PROTEIN / V-ATPase / synaptic vesicle / V0only V-ATPase |