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
AUTHORS (9)
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.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (75)
CITATIONS (148)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....