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bioRxiv · 10.1101/168518

Remodeling of ER-exit sites initiates a membrane supply pathway forautophagosome biogenesis

Ge, L.·Zhang, M.·Kenny, S.·Liu, D.·Maeda, M.·Saito, K.·Marthur, A.·Xu, K.·Schekman, R.
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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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Ge, L., Zhang, M., Kenny, S., Liu, D., Maeda, M., Saito, K., Marthur, A., Xu, K., Schekman, R.. 2017-07-25. Remodeling of ER-exit sites initiates a membrane supply pathway forautophagosome biogenesis. https://doi.org/10.1101/168518

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