The link between autophagy and secretion: a story of multitasking proteins

Abstract

The secretory and autophagy pathways can be thought of as the biosynthetic (i.e., anabolic) and degradative (i.e., catabolic) branches of the endomembrane system. In analogy to anabolic and catabolic pathways in metabolism, there is mounting evidence that the secretory and autophagy pathways are intimately linked and that certain regulatory elements are shared between them. Here we highlight the parallels and points of intersection between these two evolutionarily highly conserved and fundamental endomembrane systems. The intersection of these pathways may play an important role in remodeling membranes during cellular stress.

FIGURE 1:

Schematic representations of selected modes of cross-talk between autophagy and the secretory pathway. Right, the small GTPase Ypt1/Rab1 regulates the tethering of ER-derived, COPII-coated vesicles to the Golgi in rich medium. During starvation, however, Sec24 is phosphorylated, which promotes the fusion of COPII vesicles with Atg9 vesicles to regulate autophagosome abundance. Middle, growth factors and nutrients signal to the ERES regulator SEC16A. The autophagy-initiating kinases ULK1/2 are also activated by nutrient signaling and phosphorylate SEC16A. Finally (middle, bottom), the autophagy-regulating protein TECPR2 regulates COPII carrier biogenesis in a manner that depends on LC3C, thereby bridging secretion and autophagy.