Endosomal LC3C-pathway selectively targets plasma membrane cargo for autophagic degradation.
In: Nature Communications, Jg. 13 (2022-07-02), Heft 1, S. 1-16
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Zugriff:
Autophagy selectively targets cargo for degradation, yet mechanistic understanding remains incomplete. The ATG8-family plays key roles in autophagic cargo recruitment. Here by mapping the proximal interactome of ATG8-paralogs, LC3B and LC3C, we uncover a LC3C-Endocytic-Associated-Pathway (LEAP) that selectively recruits plasma-membrane (PM) cargo to autophagosomes. We show that LC3C localizes to peripheral endosomes and engages proteins that traffic between PM, endosomes and autophagosomes, including the SNARE-VAMP3 and ATG9, a transmembrane protein essential for autophagy. We establish that endocytic LC3C binds cargo internalized from the PM, including the Met receptor tyrosine kinase and transferrin receptor, and is necessary for their recruitment into ATG9 vesicles targeted to sites of autophagosome initiation. Structure-function analysis identified that LC3C-endocytic localization and engagement with PM-cargo requires the extended carboxy-tail unique to LC3C, the TBK1 kinase, and TBK1-phosphosites on LC3C. These findings identify LEAP as an unexpected LC3C-dependent pathway, providing new understanding of selective coupling of PM signalling with autophagic degradation. Autophagy can selectively target cargo for degradation. Here the authors map the proximal interactome of ATG8-paralogs LC3B and LC3C uncovering an LC3C-Endocytic-Associated-Pathway that selectively recruits internalized plasma membrane cargo, Met and transferrin receptors, to nascent autophagosomes. [ABSTRACT FROM AUTHOR]
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Titel: |
Endosomal LC3C-pathway selectively targets plasma membrane cargo for autophagic degradation.
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Autor/in / Beteiligte Person: | Coelho, Paula P. ; Hesketh, Geoffrey G. ; Pedersen, Annika ; Kuzmin, Elena ; Fortier, Anne-Marie N. ; Bell, Emily S. ; Ratcliffe, Colin D. H. ; Gingras, Anne-Claude ; Park, Morag |
Zeitschrift: | Nature Communications, Jg. 13 (2022-07-02), Heft 1, S. 1-16 |
Veröffentlichung: | 2022 |
Medientyp: | academicJournal |
ISSN: | 2041-1723 (print) |
DOI: | 10.1038/s41467-022-31465-3 |
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