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A Translocation Pathway for Vesicle-Mediated Unconventional Protein Secretion.
Cell ( IF 45.5 ) Pub Date : 2020-04-08 , DOI: 10.1016/j.cell.2020.03.031 Min Zhang 1 , Lei Liu 1 , Xubo Lin 2 , Yang Wang 1 , Ying Li 1 , Qing Guo 1 , Shulin Li 1 , Yuxin Sun 1 , Xuan Tao 1 , Di Zhang 1 , Xiachen Lv 1 , Li Zheng 1 , Liang Ge 1
Cell ( IF 45.5 ) Pub Date : 2020-04-08 , DOI: 10.1016/j.cell.2020.03.031 Min Zhang 1 , Lei Liu 1 , Xubo Lin 2 , Yang Wang 1 , Ying Li 1 , Qing Guo 1 , Shulin Li 1 , Yuxin Sun 1 , Xuan Tao 1 , Di Zhang 1 , Xiachen Lv 1 , Li Zheng 1 , Liang Ge 1
Affiliation
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Many cytosolic proteins lacking a signal peptide, called leaderless cargoes, are secreted through unconventional secretion. Vesicle trafficking is a major pathway involved. It is unclear how leaderless cargoes enter into the vesicle. Here, we find a translocation pathway regulating vesicle entry and secretion of leaderless cargoes. We identify TMED10 as a protein channel for the vesicle entry and secretion of many leaderless cargoes. The interaction of TMED10 C-terminal region with a motif in the cargo accounts for the selective release of the cargoes. In an in vitro reconstitution assay, TMED10 directly mediates the membrane translocation of leaderless cargoes into the liposome, which is dependent on protein unfolding and enhanced by HSP90s. In the cell, TMED10 localizes on the endoplasmic reticulum (ER)-Golgi intermediate compartment and directs the entry of cargoes into this compartment. Furthermore, cargo induces the formation of TMED10 homo-oligomers which may act as a protein channel for cargo translocation.
中文翻译：
囊泡介导的非常规蛋白质分泌的易位途径。
许多缺乏信号肽的胞质蛋白，称为无前导货物，是通过非常规分泌方式分泌的。囊泡运输是涉及的主要途径。目前尚不清楚无领导者的货物如何进入囊泡。在这里，我们发现了一条调节小泡进入和无引线货物分泌的易位途径。我们将TMED10鉴定为许多无领导物的囊泡进入和分泌的蛋白质通道。TMED10 C末端区域与货物中的图案的相互作用说明了货物的选择性释放。在体外重建测定中，TMED10直接介导无前导货物进入脂质体的膜转位，这取决于蛋白的解折叠并由HSP90s增强。在牢房里 TMED10位于内质网（ER）-高尔基体中间隔间，并引导货物进入该隔间。此外，货物诱导形成TMED10同源寡聚体，其可以充当货物转运的蛋白质通道。
更新日期：2020-04-08
中文翻译：
囊泡介导的非常规蛋白质分泌的易位途径。
许多缺乏信号肽的胞质蛋白，称为无前导货物，是通过非常规分泌方式分泌的。囊泡运输是涉及的主要途径。目前尚不清楚无领导者的货物如何进入囊泡。在这里，我们发现了一条调节小泡进入和无引线货物分泌的易位途径。我们将TMED10鉴定为许多无领导物的囊泡进入和分泌的蛋白质通道。TMED10 C末端区域与货物中的图案的相互作用说明了货物的选择性释放。在体外重建测定中，TMED10直接介导无前导货物进入脂质体的膜转位，这取决于蛋白的解折叠并由HSP90s增强。在牢房里 TMED10位于内质网（ER）-高尔基体中间隔间，并引导货物进入该隔间。此外，货物诱导形成TMED10同源寡聚体，其可以充当货物转运的蛋白质通道。
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