UCSF

The Golgi reassembly stacking proteins (GRASPs) have fascinated the scientific community due to their myriad functions throughout the cell. While originally identified as required factors for in vitro stacking of Golgi cisternae,1,2 GRASPs have also been implicated in autophagy and linked to the ER-Golgi interface, although the underlying mechanisms and biological significance have not been fully delineated. To better understand mammalian GRASP55, I leveraged genetic inhibition of GRASP55 and found that loss of GRASP55 was associated with both increased early-stage autophagy and impaired late-stage autophagy, suggesting that GRASP55 both inhibits and promotes autophagy at different steps. I also found that loss of GRASP55 phenocopied the effects of starvation on increasing colocalization of early secretory markers, suggesting that GRASP55 negatively regulates coalescence of the early secretory pathway. Interestingly, GRASP55 was not degraded during starvation, but the presence of GRASP55 dimers was enhanced by starvation, raising the possibility that the dimerization status of GRASP55 directs its functions in autophagy and secretory marker colocalization during starvation. Proximity-dependent biotinylation combined with mass spectrometry led us to identify a GRASP55 proximal interactome that was enriched in ER-Golgi interface proteins. Overall, these findings shed light on the intersections between GRASP55, autophagy, and the ER-Golgi interface.