Remodeling of ER‐exit sites initiates a membrane supply pathway for autophagosome biogenesis. (28th July 2017)

• Record Type: Journal Article
• Authors: Ge, Liang; Zhang, Min; Kenny, Samuel J; Liu, Dawei; Maeda, Miharu; Saito, Kota; Mathur, Anandita; Xu, Ke; Schekman, Randy
• Is Part Of: EMBO reports. Volume 18:Number 9(2017)
• Page Start: 1586
• Page End: 1603
• Publication Date: 2017-07-28
• Subjects: autophagosome -- autophagy -- COPII -- ER‐exit sites -- FIP200; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201744559
• Languages: English
• ISSNs: 1469-221X

Abstract

Abstract: 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. Synopsis: Autophagosome biogenesis requires membrane supply from the endomembrane system, the process of which is poorly understood. This study shows that a starvation‐induced remodeling of the ER‐exit sites, dependent on CTAGE5 and FIP200, initiates the membrane supply process by promoting the relocation of SEC12 to the ERGIC, an essential step for generating the LC3 lipidation membrane from the ERGIC. Starvation induces remodeling of the ER‐exit sites positive for SEC12 (SEC12‐ERES). CTAGE5 is required for the remodeling of the SEC12‐ERES and the relocation of SEC12 to the ERGIC and modulates autophagosome biogenesis. FIP200 facilitates the remodeling of the SEC12‐ERES by forming a complex with SEC12, which is distinct from the ULK/FIP200/ATG13/ATG101 complex on the phagophore assembly site. Abstract : Autophagosome biogenesis requires membrane supply from the endomembrane system. A starvation‐induced remodeling of the ER‐exit sites, dependent on CTAGE5 and FIP200, initiates the membrane supply process by promoting the relocation of SEC12 to the ERGIC, an essential step for generating the LC3 lipidation membrane.