Remodeling of ER‐exit sites initiates a membrane supply pathway for autophagosome biogenesis |
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| Authors: | Liang Ge Min Zhang Samuel J Kenny Dawei Liu Miharu Maeda Kota Saito Anandita Mathur Ke Xu Randy Schekman |
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| Institution: | 1. Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA;2. Department of Chemistry, University of California, Berkeley, CA, USA;3. Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan |
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| 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. |
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| Keywords: | autophagosome autophagy
COPII
ER‐exit sites FIP200 |
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