Autophagosomal YKT6 is required for fusion with lysosomes independently of syntaxin 17.
Autophagosomal YKT6 is required for fusion with lysosomes independently of syntaxin 17.
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DOI：
10.1083/jcb.201712058
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发表时间：
2018-08-06
期刊：
影响因子：
--
通讯作者：
Mizushima N
中科院分区：
文献类型：
--
作者：
Matsui T;Jiang P;Nakano S;Sakamaki Y;Yamamoto H;Mizushima N
Matsui等人将YKT 6鉴定为新的自噬体陷阱蛋白。YKT 6是自噬体-溶酶体融合所必需的，独立于STX 17，一种已知的自噬体陷阱。大自噬是一种进化上保守的分解代谢机制，其使用自噬体将细胞内成分递送到溶酶体。为了实现降解，溶酶体必须与封闭的自噬体融合。我们先前报道了可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）蛋白syntaxin（STX）17易位到自噬体介导与溶酶体的融合。在这项研究中，我们报告了另一种机制。我们发现自噬体-溶酶体融合在一定程度上甚至在STX 17敲除（KO）的HeLa细胞中保留。通过筛选其他人类SNARE，我们确定YKT 6为一种新的自噬体SNARE蛋白。耗尽YKT 6抑制自噬体-溶酶体融合部分在野生型和完全在STX 17 KO细胞，表明YKT 6和STX 17是独立的融合所需的。YKT 6与SNAP 29和溶酶体STX 7形成SNARE复合物，这两者都是自噬体融合所需的。YKT 6向自噬体的募集依赖于其N-末端长蛋白结构域，而不是C-末端棕榈酰化和法尼基化，这对于其高尔基体定位是必不可少的。这些发现表明两个独立的SNARE复合物介导自噬体-溶酶体融合。
Matsui et al. identify YKT6 as a novel autophagosomal SNARE protein. YKT6 is required for autophagosome–lysosome fusion independently of STX17, a known autophagosomal SNARE. Macroautophagy is an evolutionarily conserved catabolic mechanism that delivers intracellular constituents to lysosomes using autophagosomes. To achieve degradation, lysosomes must fuse with closed autophagosomes. We previously reported that the soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) protein syntaxin (STX) 17 translocates to autophagosomes to mediate fusion with lysosomes. In this study, we report an additional mechanism. We found that autophagosome–lysosome fusion is retained to some extent even in STX17 knockout (KO) HeLa cells. By screening other human SNAREs, we identified YKT6 as a novel autophagosomal SNARE protein. Depletion of YKT6 inhibited autophagosome–lysosome fusion partially in wild-type and completely in STX17 KO cells, suggesting that YKT6 and STX17 are independently required for fusion. YKT6 formed a SNARE complex with SNAP29 and lysosomal STX7, both of which are required for autophagosomal fusion. Recruitment of YKT6 to autophagosomes depends on its N-terminal longin domain but not on the C-terminal palmitoylation and farnesylation that are essential for its Golgi localization. These findings suggest that two independent SNARE complexes mediate autophagosome–lysosome fusion.
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影响因子：
64.8
作者：
Diao, Jiajie;Liu, Rong;Rong, Yueguang;Zhao, Minglei;Zhang, Jing;Lai, Ying;Zhou, Qiangjun;Wilz, Livia M.;Li, Jianxu;Vivona, Sandro;Pfuetzner, Richard A.;Brunger, Axel T.;Zhong, Qing
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DOI：
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发表时间：
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期刊：
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DOI：
10.1083/jcb.201412046
发表时间：
2015-05-11
期刊：
The Journal of cell biology
影响因子：
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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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作者：
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