GRASP55 restricts early-stage autophagy and regulates spatial organization of the early secretory network

Biology Open

Jennifer Y. Liu¹  Arun P. Wiita²  Hector H. Huang²  Yu-Hsiu Tony Lin²  Andrew M. Leidal³  Jordan Ye³  Jayanta Debnath³ 

[1] Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, CA 94143, USA;Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143, USA;Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA;

关键词: autophagy;    grasp55;    cell biology;   

DOI  :  10.1242/bio.058736

来源: DOAJ

【 摘 要 】

There is great interest in understanding the cellular mechanisms controlling autophagy, a tightly regulated catabolic and stress-response pathway. Prior work has uncovered links between autophagy and the Golgi reassembly stacking protein of 55 kDa (GRASP55), but their precise interrelationship remains unclear. Intriguingly, both autophagy and GRASP55 have been functionally and spatially linked to the endoplasmic reticulum (ER)­­-Golgi interface, broaching this compartment as a site where GRASP55 and autophagy may intersect. Here, we uncover that loss of GRASP55 enhances LC3 puncta formation, indicating that GRASP55 restricts autophagosome formation. Additionally, using proximity-dependent biotinylation, we identify a GRASP55 proximal interactome highly associated with the ER-Golgi interface. Both nutrient starvation and loss of GRASP55 are associated with coalescence of early secretory pathway markers. In light of these findings, we propose that GRASP55 regulates spatial organization of the ER-Golgi interface, which suppresses early autophagosome formation.

【 授权许可】

Unknown