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A conserved ATG2‐GABARAP family interaction is critical for phagophore formation
Author(s) -
Bozic Mihaela,
van den Bekerom Luuk,
Milne Beth A,
Goodman Nicola,
Roberston Lisa,
Prescott Alan R,
Macartney Thomas J,
Dawe Nina,
McEwan David G
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201948412
Subject(s) - microbiology and biotechnology , biology , genetics
The intracellular trafficking pathway, macroautophagy, is a recycling and disposal service that can be upregulated during periods of stress to maintain cellular homeostasis. An essential phase is the elongation and closure of the phagophore to seal and isolate unwanted cargo prior to lysosomal degradation. Human ATG 2A and ATG 2B proteins, through their interaction with WIPI proteins, are thought to be key players during phagophore elongation and closure, but little mechanistic detail is known about their function. We have identified a highly conserved motif driving the interaction between human ATG 2 and GABARAP proteins that is in close proximity to the ATG 2‐ WIPI 4 interaction site. We show that the ATG 2A‐ GABARAP interaction mutants are unable to form and close phagophores resulting in blocked autophagy, similar to ATG 2A/ ATG 2B double‐knockout cells. In contrast, the ATG 2A‐ WIPI 4 interaction mutant fully restored phagophore formation and autophagy flux, similar to wild‐type ATG 2A. Taken together, we provide new mechanistic insights into the requirements for ATG 2 function at the phagophore and suggest that an ATG 2‐ GABARAP / GABARAP ‐L1 interaction is essential for phagophore formation, whereas ATG 2‐ WIPI 4 interaction is dispensable.