Abstract
BackgroundAutophagy is an inducible autodigestive process that allows cells to recycle proteins and other materials for survival during stress and nutrient deprived conditions. The kinase ULK1 is required to activate this process. ULK1 phosphorylates a number of target proteins and regulates many cellular processes including the early secretory pathway. Recently, ULK1 has been demonstrated to phosphorylate Sec16 and affects the transport of serotonin transporter at the ER exit sites (ERES), but whether ULK1 may affect the transport of other cargo proteins and general secretion has not been fully addressed.ResultsIn this study, we identified Sec23A, a component of the COPII vesicle coat, as a target of ULK1 phosphorylation. Elevated autophagy, induced by amino acid starvation, rapamycin, or overexpression of ULK1 caused aggregation of the ERES, a region of the ER dedicated for the budding of COPII vesicles. Transport of cargo proteins was also inhibited under these conditions and was retained at the ERES. ULK1 phosphorylation of Sec23A reduced the interaction between Sec23A and Sec31A. We identified serine 207, serine 312 and threonine 405 on Sec23A as ULK1 phosphorylation sites. Among these residues, serine 207, when changed to phospho-deficient and phospho-mimicking mutants, most faithfully recapitulated the above-mentioned effects of ULK1 phospho-regulation.ConclusionThese findings identify Sec23A as a new target of ULK1 and uncover a mechanism of coordinating intracellular protein transport and autophagy.
Highlights
Autophagy is an inducible autodigestive process that allows cells to recycle proteins and other materials for survival during stress and nutrient deprived conditions
To investigate whether autophagy causes any change to the early secretory pathway in mammalian cells, we found that ER exit sites (ERES) morphology is different in cells undergoing active autophagy and protein intracellular transport is inhibited at the ERESs
ULK1 interacts with Sec23A Recently it was reported that the substrate of TRAPPIII, Rab small GTPase Ypt1, interacted with Atg1 for activation of autophagy at the preautophagosomal structure (PAS) [24]
Summary
Autophagy is an inducible autodigestive process that allows cells to recycle proteins and other materials for survival during stress and nutrient deprived conditions. Autophagy is an inducible lysosomal degradation process that recycles proteins and organelles to supply the cells with amino acids, lipids and energy for survival. This process is activated during stresses like amino acid starvation. Components of the COPII coat present punctate structures that decorate the ER tubules under fluorescent microscopy. These structures are defined as ERESs, where budding of COPII vesicles occurs
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