Vti1a/b regulate synaptic vesicle and dense core vesicle secretion via protein sorting at the Golgi.
Vti1a/b regulate synaptic vesicle and dense core vesicle secretion via protein sorting at the Golgi.
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DOI：
10.1038/s41467-018-05699-z
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发表时间：
2018-08-24
影响因子：
16.6
通讯作者：
Verhage M
中科院分区：
文献类型：
--
作者：
Emperador-Melero J;Huson V;van Weering J;Bollmann C;Fischer von Mollard G;Toonen RF;Verhage M
SNARE Vti 1a/1b与调节分泌有关，但它们相对于典型胞吐SNARE的作用仍然难以捉摸。在这里，我们表明，突触囊泡和致密核心囊泡（DCV）的分泌确实严重受损Vti 1a/b缺陷的神经元。介导分泌的蛋白质的突触水平降低，对于胞吐SNARE SNAP 25下降至50%。SNAP 25和DCV-货物进入轴突的递送减少，并且这些分子在高尔基体中积累。这些缺陷被Vti 1a或Vti 1b表达所挽救。在Vti 1a/b缺陷的神经元中观察到扩张的高尔基池和清晰的空泡。高尔基体内DCV-货物的正常非均匀分布丢失。货物运输出高尔基，但不是进入高尔基，受到损害。最后，逆行霍乱毒素运输，但不是分拣蛋白/Sorcs 1分布，受到影响。我们的结论是，Vti 1a/B支持调节分泌的排序分泌货物和突触分泌机械组件在高尔基体。Vti 1a和Vti 1b是参与调节分泌的SNARE蛋白。在这里，作者表明Vti 1a和Vti 1b控制高尔基体的蛋白质分选，并靶向轴突，从而间接控制突触的调节分泌。
The SNAREs Vti1a/1b are implicated in regulated secretion, but their role relative to canonical exocytic SNAREs remains elusive. Here, we show that synaptic vesicle and dense-core vesicle (DCV) secretion is indeed severely impaired in Vti1a/b-deficient neurons. The synaptic levels of proteins that mediate secretion were reduced, down to 50% for the exocytic SNARE SNAP25. The delivery of SNAP25 and DCV-cargo into axons was decreased and these molecules accumulated in the Golgi. These defects were rescued by either Vti1a or Vti1b expression. Distended Golgi cisternae and clear vacuoles were observed in Vti1a/b-deficient neurons. The normal non-homogeneous distribution of DCV-cargo inside the Golgi was lost. Cargo trafficking out of, but not into the Golgi, was impaired. Finally, retrograde Cholera Toxin trafficking, but not Sortilin/Sorcs1 distribution, was compromised. We conclude that Vti1a/b support regulated secretion by sorting secretory cargo and synaptic secretion machinery components at the Golgi. Vti1a and Vti1b are SNARE proteins implicated in regulated secretion. Here the authors show that Vti1a and Vti1b control protein sorting at the Golgi, and targeting to the axon, and thereby indirectly control regulated secretion at the synapse.
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影响因子：
11.4
作者：
Cruz-Garcia, David;Ortega-Bellido, Maria;Malhotra, Vivek
通讯作者：
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影响因子：
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作者：
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影响因子：
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Lee, FS
影响因子：
48
作者：
Boncompain, Gaelle;Divoux, Severine;Perez, Franck
通讯作者：
Perez, Franck
影响因子：
16.2
作者：
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通讯作者：
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