PMID- 29129923 OWN - NLM STAT- MEDLINE DCOM- 20180911 LR - 20181113 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 8 IP - 1 DP - 2017 Nov 13 TI - Ist1 regulates ESCRT-III assembly and function during multivesicular endosome biogenesis in Caenorhabditis elegans embryos. PG - 1439 LID - 10.1038/s41467-017-01636-8 [doi] LID - 1439 AB - 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. FAU - Frankel, E B AU - Frankel EB AD - Department of Biomolecular Chemistry, University of Wisconsin-Madison School of Medicine and Public Health, 440 Henry Mall, Madison, WI, 53706, USA. FAU - Shankar, Raakhee AU - Shankar R AD - Department of Biomolecular Chemistry, University of Wisconsin-Madison School of Medicine and Public Health, 440 Henry Mall, Madison, WI, 53706, USA. FAU - Moresco, James J AU - Moresco JJ AD - The Scripps Research Institute, 10550 North Torrey Pines Rd., Department of Chemical Physiology, La Jolla, CA, 92037, USA. FAU - Yates, John R 3rd AU - Yates JR 3rd AUID- ORCID: 0000-0001-5267-1672 AD - The Scripps Research Institute, 10550 North Torrey Pines Rd., Department of Chemical Physiology, La Jolla, CA, 92037, USA. FAU - Volkmann, Niels AU - Volkmann N AD - Bioinformatics and Structural Biology Program, Sanford-Burnham Medical Research Institute, 10901N Torrey Pines Rd, La Jolla, CA, 92037, USA. FAU - Audhya, Anjon AU - Audhya A AUID- ORCID: 0000-0002-7828-5152 AD - Department of Biomolecular Chemistry, University of Wisconsin-Madison School of Medicine and Public Health, 440 Henry Mall, Madison, WI, 53706, USA. audhya@wisc.edu. LA - eng GR - P41 GM103533/GM/NIGMS NIH HHS/United States GR - R01 GM115972/GM/NIGMS NIH HHS/United States GR - T32 GM007215/GM/NIGMS NIH HHS/United States GR - R01 GM088151/GM/NIGMS NIH HHS/United States GR - R01 GM110567/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20171113 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Caenorhabditis elegans Proteins) RN - 0 (Endosomal Sorting Complexes Required for Transport) RN - 0 (IST-1 protein, C elegans) RN - 0 (RNA, Small Interfering) RN - 0 (Vesicular Transport Proteins) SB - IM MH - Adaptor Proteins, Signal Transducing/genetics/*metabolism MH - Animals MH - Caenorhabditis elegans/*embryology MH - Caenorhabditis elegans Proteins/genetics/*metabolism MH - Cell Membrane/*metabolism MH - Endosomal Sorting Complexes Required for Transport/biosynthesis/genetics/*metabolism MH - Multivesicular Bodies/*metabolism MH - Oocytes/growth & development MH - Protein Transport/physiology MH - RNA Interference MH - RNA, Small Interfering/genetics MH - Vesicular Transport Proteins/*metabolism PMC - PMC5682282 COIS- The authors declare no competing financial interests. EDAT- 2017/11/14 06:00 MHDA- 2018/09/12 06:00 PMCR- 2017/11/13 CRDT- 2017/11/14 06:00 PHST- 2017/03/23 00:00 [received] PHST- 2017/10/03 00:00 [accepted] PHST- 2017/11/14 06:00 [entrez] PHST- 2017/11/14 06:00 [pubmed] PHST- 2018/09/12 06:00 [medline] PHST- 2017/11/13 00:00 [pmc-release] AID - 10.1038/s41467-017-01636-8 [pii] AID - 1636 [pii] AID - 10.1038/s41467-017-01636-8 [doi] PST - epublish SO - Nat Commun. 2017 Nov 13;8(1):1439. doi: 10.1038/s41467-017-01636-8.