Dedicated SNAREs and specialized TRIM cargo receptors mediate secretory autophagy
Dedicated SNAREs and specialized TRIM cargo receptors mediate secretory autophagy
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DOI：
10.15252/embj.201695081
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发表时间：
2017-01-04
期刊：
影响因子：
11.4
通讯作者：
Deretic, Vojo
中科院分区：
文献类型：
--
作者：
Kimura, Tomonori;Jia, Jingyue;Deretic, Vojo
自噬是将细胞质组分递送到溶酶体进行降解的过程。然而，自噬可能在非常规的无前导细胞溶质蛋白的分泌中发挥作用。分泌性自噬是如何从降解性自噬中分化出来的仍不清楚。在这里，我们表明，在响应溶酶体损伤，原型胞质分泌性自噬货物IL-1被识别的专门的分泌性自噬货物受体TRIM 16，该受体与R-SNARE Sec 22 b相互作用，招募货物的LC 3-II+隔离膜。货物分泌不受突触融合蛋白17下调的影响，突触融合蛋白17是一种促进自噬体-溶酶体融合和货物降解的SNARE。相反，Sec 22 b与质膜突触融合蛋白3和突触融合蛋白4以及SNAP-23和SNAP-29组合完成货物分泌。因此，分泌性自噬利用专门的细胞溶质货物受体和专用的SNARE系统。其他非常规分泌的货物，如铁蛋白，通过相同的途径分泌。
Autophagy is a process delivering cytoplasmic components to lysosomes for degradation. Autophagy may, however, play a role in unconventional secretion of leaderless cytosolic proteins. How secretory autophagy diverges from degradative autophagy remains unclear. Here we show that in response to lysosomal damage, the prototypical cytosolic secretory autophagy cargo IL-1 is recognized by specialized secretory autophagy cargo receptor TRIM16 and that this receptor interacts with the R-SNARE Sec22b to recruit cargo to the LC3-II+ sequestration membranes. Cargo secretion is unaffected by downregulation of syntaxin 17, a SNARE promoting autophagosome-lysosome fusion and cargo degradation. Instead, Sec22b in combination with plasma membrane syntaxin 3 and syntaxin 4 as well as SNAP-23 and SNAP-29 completes cargo secretion. Thus, secretory autophagy utilizes a specialized cytosolic cargo receptor and a dedicated SNARE system. Other unconventionally secreted cargo, such as ferritin, is secreted via the same pathway.