Abstract
Endoplasmic Reticulum (ER)-derived COPII coated vesicles constitutively transport secretory cargo to the Golgi. However, during starvation-induced stress, COPII vesicles have been implicated as a membrane source for autophagosomes, distinct organelles that engulf cellular components for degradation by macroautophagy (hereafter called autophagy). How cells regulate core trafficking machinery to fulfill dramatically different cellular roles in response to environmental cues is unknown. Here we show that phosphorylation of conserved amino acids on the membrane-distal surface of the Saccharomyces cerevisiae COPII cargo adaptor, Sec24, reprograms COPII vesicles for autophagy. We also show casein kinase 1 (Hrr25) is a key kinase that phosphorylates this regulatory surface. During autophagy, Sec24 phosphorylation regulates autophagosome number and its interaction with the C-terminus of Atg9, a component of the autophagy machinery required for autophagosome initiation. We propose that the acute need to produce autophagosomes during starvation drives the interaction of Sec24 with Atg9 to increase autophagosome abundance.
Highlights
Autophagy is a highly conserved catabolic process that uses membrane traffic to target proteins and organelles for degradation
To address whether coat phosphorylation allows COPII vesicles to function in autophagy versus ERGolgi traffic, we purified the COPII inner coat from yeast cells induced for autophagy
COPII vesicles formed in vitro with Sec24-S730A/S735A showed normal capture of Sed5 and other cargo, whereas those formed with Sec24-S730D/S735D contained reduced amounts of Sed5 and were modestly impaired in their fusion efficiency with the Golgi (Figure 1—figure supplement 1B,C)
Summary
Autophagy is a highly conserved catabolic process that uses membrane traffic to target proteins and organelles for degradation. When cells are starved for nutrients, autophagy is quickly upregulated. This upregulation leads to a dramatic intracellular reorganization to meet the high demand for membrane required to form autophagosomes, distinct organelles that target cellular components for degradation (Nakatogawa et al, 2009). Induction of autophagy leads to the formation of a double-membrane structure, called the isolation membrane, that forms adjacent to a pre-autophagosome structure (PAS) where autophagy related proteins (Atg) are recruited in a hierarchical manner (Nakatogawa et al, 2009). As the isolation membrane expands, it engulfs cytoplasmic proteins and organelles targeted for degradation before it seals to form an autophagosome.
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