Ist1 regulates ESCRT-III assembly and function during multivesicular endosome biogenesis in Caenorhabditis elegans embryos.
Ist1 regulates ESCRT-III assembly and function during multivesicular endosome biogenesis in Caenorhabditis elegans embryos.
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DOI：
10.1038/s41467-017-01636-8
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发表时间：
2017-11-13
影响因子：
16.6
通讯作者：
Audhya A
中科院分区：
文献类型：
--
作者：
Frankel EB;Shankar R;Moresco JJ;Yates JR 3rd;Volkmann N;Audhya A
大多数整体膜蛋白的降解是由运输所需的内体分选复合体（ESCRT）机制指导的，该机制选择性地将泛素修饰的货物靶向到多泡内体（MVEs）的腔内囊泡（ILVs）中。为了更好地理解escrt介导的ilv形成的机制，我们利用了秀丽隐杆线虫卵细胞向胚胎转变过程中MVEs的快速新生生物发生。与之前的模型表明ilv是单独形成的相反，我们证明了它们在内部化之后仍然彼此相连，认为它们从稳定的子域连续萌芽。此外，我们发现膜弯曲和ILV的形成在体内由ESCRT- iii复合物以Ist1调节的方式特异性地指导，这促进了ESCRT- iii的组装并抑制了上游ESCRT成分并入ILV。我们的研究结果强调了ESCRT-III在膜重塑、货物选择和货物保留方面的基本作用，这些作用重复地最大化ILV的形成速率。秀丽隐杆线虫在卵母细胞向胚胎转变的过程中，多泡核内体（MVEs）迅速形成。通过实时成像和电子显微镜，作者发现ESCRT-III亚基Ist1是秀丽隐杆线虫早期胚胎正常MVE生物发生所必需的。
Degradation of most integral membrane proteins is directed by the endosomal sorting complex required for transport (ESCRT) machinery, which selectively targets ubiquitin-modified cargoes into intralumenal vesicles (ILVs) within multivesicular endosomes (MVEs). To better understand the mechanisms underlying ESCRT-mediated formation of ILVs, we exploited the rapid, de novo biogenesis of MVEs during the oocyte-to-embryo transition in C. elegans. In contrast to previous models suggesting that ILVs form individually, we demonstrate that they remain tethered to one another subsequent to internalization, arguing that they bud continuously from stable subdomains. In addition, we show that membrane bending and ILV formation are directed specifically by the ESCRT-III complex in vivo in a manner regulated by Ist1, which promotes ESCRT-III assembly and inhibits the incorporation of upstream ESCRT components into ILVs. Our findings underscore essential actions for ESCRT-III in membrane remodeling, cargo selection, and cargo retention, which act repetitively to maximize the rate of ILV formation. During the oocyte-to-embryo transition in C. elegans, multivesicular endosomes (MVEs) are formed rapidly. Using live imaging and electron microscopy, the authors here show that the ESCRT-III subunit Ist1 is required for normal MVE biogenesis in the early C. elegans embryo.
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影响因子：
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