RT Journal Article
SR Electronic
T1 Remodeling of ER-exit sites initiates a membrane supply pathway for autophagosome biogenesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 168518
DO 10.1101/168518
A1 Liang Ge
A1 Min Zhang
A1 Samuel J Kenny
A1 Dawei Liu
A1 Miharu Maeda
A1 Kota Saito
A1 Anandita Mathur
A1 Ke Xu
A1 Randy Schekman
YR 2017
UL http://biorxiv.org/content/early/2017/07/25/168518.abstract
AB 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.