Synaptophysin I selectively specifies the exocytic pathway of synaptobrevin 2/VAMP2
Synaptophysin I selectively specifies the exocytic pathway of synaptobrevin 2/VAMP2
复制标题
DOI：
10.1042/bj20061907
复制
发表时间：
2007-06-15
影响因子：
4.1
通讯作者：
Valtorta, Flavia
中科院分区：
文献类型：
--
作者：
Bonanomi, Dario;Rusconi, Laura;Valtorta, Flavia
突触囊泡的生物发生和再循环伴随着保存所涉及的隔室的分子组成的分选过程。在本研究中，我们已经解决了靶向突触泡蛋白2/VAMP 2（囊泡相关膜蛋白2），突触囊泡融合机制的关键组成部分，在异型背景下，其排序不混淆其他神经元特异性分子的存在。异位表达的突触素I与VAMP 2相互作用，并将其默认的表面靶向改变为突出的囊泡分布，对其他膜蛋白的靶向没有影响。蛋白质-蛋白质相互作用不足以控制VAMP 2分选，其由突触体蛋白I的C-末端结构域介导。突触素I在表面递送之前指导VAMP 2分选到囊泡，而不影响VAMP 2内吞作用。与此一致，发动蛋白和α-SNAP（可溶性N-乙基马来酰亚胺敏感性融合蛋白-附着蛋白）突变体，阻止在质膜上的运输不消除突触体蛋白I对VAMP 2分选的影响。这些结果表明，突触囊泡蛋白的分选决定簇可以独立于神经元的上下文进行操作，并暗示VAMP 2与突触体蛋白I在突触囊泡生物发生途径的规范中的关联。
Biogenesis and recycling of synaptic vesicles are accompanied by sorting processes that preserve the molecular composition of the compartments involved. In the present study, we have addressed the targeting of synaptobrevin 2/VAMP2 (vesicle-associated membrane protein 2), a critical component of the synaptic vesicle-fusion machinery, in a heterotypic context where its sorting is not confounded by the presence of other neuron-specific molecules. Ectopically expressed synaptophysin I interacts with VAMP2 and alters its default surface targeting to a prominent vesicular distribution, with no effect on the targeting of other membrane proteins. Protein-protein interaction is not sufficient for the control of VAMP2 sorting, which is mediated by the C-terminal domain of synaptophysin I. Synaptophysin I directs the sorting of VAMP2 to vesicles before surface delivery, without influencing VAMP2 endocytosis. Consistent with this, dynamin and a-SNAP(soluble N-ethylmaleimide-sensitive fusion protein-attachment protein) mutants which block trafficking at the plasma membrane do not abrogate the effect of synaptophysin I on VAMP2 sorting. These results indicate that the sorting determinants of synaptic vesicle proteins can operate independently of a neuronal context and implicate the association of VAMP2 with synaptophysin I in the specification of the pathway of synaptic vesicle biogenesis.