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Contact (Thousand Oaks). 2018 Jan-Dec;1. doi: 10.1177/2515256418819936. Epub 2018 Dec 21.

The rod-shaped ATG2A-WIPI4 complex tethers membranes in vitro.

Author information

1
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
2
Present address: Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794, USA.

Abstract

The autophagosome precursor membrane, termed the "isolation membrane" or "phagophore," emerges adjacent to a PI3P-enriched transient subdomain of the ER called the "omegasome," thereafter expanding to engulf cytoplasmic content. Uncovering the molecular events that occur in the vicinity of the omegasome during phagophore biogenesis is imperative for understanding the mechanisms involved in this critical step of the autophagy pathway. We recently characterized the ATG2A-WIPI4 complex, one of the factors that localize to the omegasome and play a critical role in mediating phagophore expansion. Our structural and biochemical studies revealed that ATG2A is a rod-shaped protein with membrane-interacting properties at each end, endowing ATG2A with membrane-tethering capability. Association of the PI3P-binding protein WIPI4 at one of the ATG2A tips enables the ATG2A-WIPI4 complex to specifically tether PI3P-containing membranes to non-PI3P-containing membranes. We proposed models for the ATG2A-WIPI4 complex-mediated membrane associations between the omegasome and surrounding membranes, including the phagophore edge, the ER, ATG9 vesicles, and COPII vesicles.

KEYWORDS:

ATG18; ATG2; WIPI; autophagosome; autophagy; membrane tethering

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