Journal
EMBO REPORTS
Volume 18, Issue 9, Pages 1586-1603Publisher
WILEY
DOI: 10.15252/embr.201744559
Keywords
autophagosome; autophagy; COPII; ER-exit sites; FIP200
Categories
Funding
- NIH [K99/R00]
- National Institute of General Medical Sciences [1K99GM114397-02]
- NSF [CHE-1554717]
- Pew Biomedical Scholars Award
- Sloan Research Fellowship
- Japan Society for the Promotion of Science (JSPS)
- Grants-in-Aid for Scientific Research [17J07885, 26440046] Funding Source: KAKEN
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Autophagosomes are double-membrane vesicles generated during autophagy. Biogenesis of the autophagosome requires membrane acquisition from intracellular compartments, the mechanisms of which are unclear. We previously found that a relocation of COPII machinery to the ER-Golgi intermediate compartment (ERGIC) generates ERGIC-derived COPII vesicles which serve as a membrane precursor for the lipidation of LC3, a key membrane component of the autophagosome. Here we employed super-resolution microscopy to show that starvation induces the enlargement of ER-exit sites (ERES) positive for the COPII activator, SEC12, and the remodeled ERES patches along the ERGIC. A SEC12 binding protein, CTAGE5, is required for the enlargement of ERES, SEC12 relocation to the ERGIC, and modulates autophagosome biogenesis. Moreover, FIP200, a subunit of the ULK protein kinase complex, facilitates the starvation-induced enlargement of ERES independent of the other subunits of this complex and associates via its C-terminal domain with SEC12. Our data indicate a pathway wherein FIP200 and CTAGE5 facilitate starvation-induced remodeling of the ERES, a prerequisite for the production of COPII vesicles budded from the ERGIC that contribute to autophagosome formation.
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