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Distinct functions ...
Distinct functions of ATG16L1 isoforms in membrane binding and LC3B lipidation in autophagy-related processes
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Lystad, Aif Hakon (författare)
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- Carlsson, Sven R (författare)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik
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de la Ballina, Laura R. (författare)
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Kauffman, Karlina J. (författare)
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Nag, Shanta (författare)
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Yoshimori, Tamotsu (författare)
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Melia, Thomas J. (författare)
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Simonsen, Anne (författare)
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(creator_code:org_t)
- 2019-02-18
- 2019
- Engelska.
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Ingår i: Nature Cell Biology. - : NATURE PUBLISHING GROUP. - 1465-7392 .- 1476-4679. ; 21:3, s. 372-383
- Relaterad länk:
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https://europepmc.or...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Covalent modification of LC3 and GABARAP proteins to phosphatidylethanolamine in the double-membrane phagophore is a key event in the early phase of macroautophagy, but can also occur on single-membrane structures. In both cases this involves transfer of LC3/GABARAP from ATG3 to phosphatidylethanolamine at the target membrane. Here we have purified the full-length human ATG12-5-ATG16L1 complex and show its essential role in LC3B/GABARAP lipidation in vitro. We have identified two functionally distinct membrane-binding regions in ATG16L1. An N-terminal membrane-binding amphipathic helix is required for LC3B lipidation under all conditions tested. By contrast, the C-terminal membrane-binding region is dispensable for canonical autophagy but essential for VPS34-independent LC3B lipidation at perturbed endosomes. We further show that the ATG16L1 C-terminus can compensate for WIPI2 depletion to sustain lipidation during starvation. This C-terminal membrane-binding region is present only in the beta-isoform of ATG16L1, showing that ATG16L1 isoforms mechanistically distinguish between different LC3B lipidation mechanisms under different cellular conditions.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biofysik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biophysics (hsv//eng)
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- ref (ämneskategori)
- art (ämneskategori)
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