Global Proximity Interactome of the Human Macroautophagy Pathway

Yi Xin Tu, Andrew M. Sydor, Etienne Coyaud, Estelle M.N. Laurent, Diana Dyer, Nora Mellouk, Jonathan St-Germain, Robert M. Vernon, Julie D. Forman-Kay, Taoyingnan Li, Rong Hua, Kexin Zhao, Neale D. Ridgway, Peter K. Kim, Brian Raught, John H. Brumell

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11 Citas (Scopus)

Resumen

Macroautophagy is a highly conserved eukaryotic cellular pathway involving the engulfment of macromolecules, organelles, and invading microbes by a double-membrane compartment and subsequent lysosomal degradation. The mechanisms that regulate macroautophagy, and the interaction of its components with other cellular pathways, have remained unclear. Here, we performed proximity-dependent biotin identification (BioID) on 39 core human macroautophagy proteins, identifying over 700 unique high confidence proximity interactors with new putative connections between macroautophagic and essential cellular processes. Of note, we identify members of the OSBPL (oxysterol binding protein like) family as Atg8-family protein interactors. We subsequently conducted comprehensive screens of the OSBPL family for LC3B-binding and roles in xenophagy and aggrephagy. OSBPL7 and OSBPL11 emerged as novel lipid transfer proteins required for macroautophagy of selective cargo. Altogether, our proximity interaction map provides a valuable resource for the study of autophagy and highlights the critical role of membrane contact site proteins in the pathway. Abbreviations: BioID: proximity-dependent biotin identification; GO: gene ontology; OSBPL: oxysterol binding protein like; VAPA: VAMP associated protein A; VAPB: VAMP associated protein B and C.

Idioma originalEnglish
PublicaciónAutophagy
DOI
EstadoAccepted/In press - 2021

Nota bibliográfica

Funding Information:
J.H.B. holds the Pitblado Chair in Cell Biology. Infrastructure for the Brumell Laboratory was provided by a John Evans Leadership Fund grant from the Canadian Foundation for Innovation and the Ontario Innovation Trust. N.M. was supported by a fellowship from the Research Training Centre at the Hospital for Sick Children. This work was supported by operating grants the Canadian Institutes of Health Research (MOP#97756; PJT#148668; FDN154329).

Publisher Copyright:
© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

ASJC Scopus Subject Areas

  • Molecular Biology
  • Cell Biology

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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