Identification of membrane curvature sensing motifs essential for VPS37A phagophore recruitment and autophagosome closure

Autor: Yansheng Ye, Xinwen Liang, Guifang Wang, Maria C. Bewley, Kouta Hamamoto, Xiaoming Liu, John M. Flanagan, Hong-Gang Wang, Yoshinori Takahashi, Fang Tian
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Communications Biology, Vol 7, Iss 1, Pp 1-12 (2024)
Druh dokumentu: article
ISSN: 2399-3642
DOI: 10.1038/s42003-024-06026-7
Popis: Abstract VPS37A, an ESCRT-I complex component, is required for recruiting a subset of ESCRT proteins to the phagophore for autophagosome closure. However, the mechanism by which VPS37A is targeted to the phagophore remains obscure. Here, we demonstrate that the VPS37A N-terminal domain exhibits selective interactions with highly curved membranes, mediated by two membrane-interacting motifs within the disordered regions surrounding its Ubiquitin E2 variant-like (UEVL) domain. Site-directed mutations of residues in these motifs disrupt ESCRT-I localization to the phagophore and result in defective phagophore closure and compromised autophagic flux in vivo, highlighting their essential role during autophagy. In conjunction with the UEVL domain, we postulate that these motifs guide a functional assembly of the ESCRT machinery at the highly curved tip of the phagophore for autophagosome closure. These results advance the notion that the distinctive membrane architecture of the cup-shaped phagophore spatially regulates autophagosome biogenesis.
Databáze: Directory of Open Access Journals
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje