Remodeling of ER ‐exit sites initiates a membrane supply pathway for autophagosome biogenesis

autophagy autophagosome ER-exit sites Vesicular Transport Proteins Autophagy-Related Proteins Golgi Apparatus Endoplasmic Reticulum 03 medical and health sciences ER‐exit sites Antigens, Neoplasm Autophagy COPII Humans FIP200 Antigens 2. Zero hunger Microscopy 0303 health sciences Membranes Organelle Biogenesis Autophagosomes Membrane Proteins Protein-Tyrosine Kinases Neoplasm Proteins Protein Transport Hela Cells Neoplasm Generic health relevance Biochemistry and Cell Biology COP-Coated Vesicles Microtubule-Associated Proteins Developmental Biology HeLa Cells
DOI: 10.15252/embr.201744559 Publication Date: 2017-07-29T00:10:26Z
ABSTRACT
AbstractAutophagosomes 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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