UBL3 modification influences protein sorting to small extracellular vesicles.
UBL3 modification influences protein sorting to small extracellular vesicles.
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DOI：
10.1038/s41467-018-06197-y
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发表时间：
2018-09-26
影响因子：
16.6
通讯作者：
Tsuchida K
中科院分区：
文献类型：
--
作者：
Ageta H;Ageta-Ishihara N;Hitachi K;Karayel O;Onouchi T;Yamaguchi H;Kahyo T;Hatanaka K;Ikegami K;Yoshioka Y;Nakamura K;Kosaka N;Nakatani M;Uezumi A;Ide T;Tsutsumi Y;Sugimura H;Kinoshita M;Ochiya T;Mann M;Setou M;Tsuchida K
外泌体是一种源自多泡体（MVBs）的小细胞外囊泡（sev），通过运输蛋白质、mrna和mirna介导细胞间通讯。然而，蛋白质被分类为sev的分子机制尚不完全清楚。在这里，我们报道了泛素样3 (UBL3)/膜锚定的Ub-fold蛋白（MUB）作为翻译后修饰（PTM）因子调节蛋白质对sev的分类。我们发现UBL3的修改对于UBL3对MVBs和sev的排序是必不可少的。我们还观察到，与野生型小鼠相比，从ubl3敲除小鼠纯化的sev中总蛋白水平降低了60%。通过蛋白质组学分析，我们发现1241个ubl3相互作用蛋白，包括Ras。我们还发现UBL3直接修饰Ras和致癌的RasG12V突变体，并且UBL3的表达通过UBL3修饰增强了RasG12V对sev的排序。总之，这些结果表明，UBL3的PTM影响了蛋白质对sev的分选。外泌体通过转运蛋白质、mrna和mirna介导细胞间的通讯，但蛋白质向外泌体分选的机制尚不清楚。在这里，作者发现泛素样3 （UBL3）通过作为翻译后修饰调节蛋白质对外泌体的分类。
Exosomes, a type of small extracellular vesicles (sEVs), derived from multivesicular bodies (MVBs), mediate cell-to-cell communication by transporting proteins, mRNAs, and miRNAs. However, the molecular mechanism by which proteins are sorted to sEVs is not fully understood. Here, we report that ubiquitin-like 3 (UBL3)/membrane-anchored Ub-fold protein (MUB) acts as a posttranslational modification (PTM) factor that regulates protein sorting to sEVs. We find that UBL3 modification is indispensable for sorting of UBL3 to MVBs and sEVs. We also observe a 60% reduction of total protein levels in sEVs purified from Ubl3-knockout mice compared with those from wild-type mice. By performing proteomics analysis, we find 1241 UBL3-interacting proteins, including Ras. We also show that UBL3 directly modifies Ras and oncogenic RasG12V mutant, and that UBL3 expression enhances sorting of RasG12V to sEVs via UBL3 modification. Collectively, these results indicate that PTM by UBL3 influences the sorting of proteins to sEVs. Exosomes mediate cell-to-cell communication by transporting proteins, mRNAs, and miRNAs but the mechanisms of protein sorting to exosomes are poorly understood. Here, the authors uncover that ubiquitin-like 3 (UBL3) regulates protein sorting to exosomes by acting as a posttranslational modification.
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DOI：
10.1073/pnas.1521230113
发表时间：
2016-02-23
影响因子：
11.1
作者：
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发表时间：
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影响因子：
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通讯作者：
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影响因子：
13.6
作者：
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通讯作者：
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影响因子：
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作者：
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