除了 MUN 结构域，Munc13 还控制着突触囊泡的引发和去引发。
Beyond the MUN domain, Munc13 controls priming and depriming of synaptic vesicles.
机构信息
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA; Department of Structural Biology, Stanford University, Stanford, CA, USA; Department of Photon Science, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA; Department of Structural Biology, Stanford University, Stanford, CA, USA; Department of Photon Science, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
出版信息
Cell Rep. 2024 May 28;43(5):114026. doi: 10.1016/j.celrep.2024.114026. Epub 2024 May 21.
Synaptic vesicle docking and priming are dynamic processes. At the molecular level, SNAREs (soluble NSF attachment protein receptors), synaptotagmins, and other factors are critical for Ca-triggered vesicle exocytosis, while disassembly factors, including NSF (N-ethylmaleimide-sensitive factor) and α-SNAP (soluble NSF attachment protein), disassemble and recycle SNAREs and antagonize fusion under some conditions. Here, we introduce a hybrid fusion assay that uses synaptic vesicles isolated from mouse brains and synthetic plasma membrane mimics. We included Munc18, Munc13, complexin, NSF, α-SNAP, and an ATP-regeneration system and maintained them continuously-as in the neuron-to investigate how these opposing processes yield fusogenic synaptic vesicles. In this setting, synaptic vesicle association is reversible, and the ATP-regeneration system produces the most synchronous Ca-triggered fusion, suggesting that disassembly factors perform quality control at the early stages of synaptic vesicle association to establish a highly fusogenic state. We uncovered a functional role for Munc13 ancillary to the MUN domain that alleviates an α-SNAP-dependent inhibition of Ca-triggered fusion.
突触囊泡的对接和引发是动态过程。在分子水平上，SNAREs（可溶性 NSF 附着蛋白受体）、突触融合蛋白和其他因子对于 Ca 触发的囊泡胞吐至关重要，而解体因子，包括 NSF（N-乙基马来酰亚胺敏感因子）和 α-SNAP（可溶性 NSF 附着蛋白），在某些条件下，解体和回收 SNAREs 并拮抗融合。在这里，我们引入了一种杂交融合测定法，该方法使用从小鼠脑中分离的突触囊泡和合成的质膜模拟物。我们包括 Munc18、Munc13、复合蛋白、NSF、α-SNAP 和一个 ATP 再生系统，并连续维持它们，就像神经元一样，以研究这些相反的过程如何产生融合性突触囊泡。在这种情况下，突触囊泡的结合是可逆的，ATP 再生系统产生最同步的 Ca 触发融合，这表明解体因子在突触囊泡结合的早期阶段进行质量控制，以建立高度融合性状态。我们发现 Munc13 的功能作用除了 MUN 结构域外，还缓解了 α-SNAP 对 Ca 触发融合的抑制作用。
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