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Remodeling of ER ‐exit sites initiates a membrane supply pathway for autophagosome biogenesis
Author(s) -
Ge Liang,
Zhang Min,
Kenny Samuel J,
Liu Dawei,
Maeda Miharu,
Saito Kota,
Mathur Anandita,
Xu Ke,
Schekman Randy
Publication year - 2017
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.201744559
Subject(s) - library science , biogenesis , chemistry , environmental ethics , philosophy , biochemistry , computer science , gene
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 LC 3, 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, SEC 12, and the remodeled ERES patches along the ERGIC . A SEC 12 binding protein, CTAGE 5, is required for the enlargement of ERES , SEC 12 relocation to the ERGIC , and modulates autophagosome biogenesis. Moreover, FIP 200, 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 SEC 12. Our data indicate a pathway wherein FIP 200 and CTAGE 5 facilitate starvation‐induced remodeling of the ERES , a prerequisite for the production of COPII vesicles budded from the ERGIC that contribute to autophagosome formation.