title: Sec24 phosphorylation regulates autophagosome abundance during nutrient deprivation.
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 theSaccharomyces cerevisiaeCOPII 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.
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States.
authors.forename: Saralin
authors.identifier: 0000-0002-9834-8683
authors.initials: S
authors.lastname: Davis
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Biological Sciences, Columbia University, New York, United States.
authors.forename: Kyle
authors.initials: K
authors.lastname: Stahmer
authors.affiliation: Department of Biological Sciences, Columbia University, New York, United States.
authors.forename: Ramya
authors.initials: R
authors.lastname: Lakshminarayan
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, San Diego, United States.|Biomolecular and Proteomics Mass Spectrometry Facility, University of California, San Diego, San Diego, United States.
authors.forename: Majid
authors.initials: M
authors.lastname: Ghassemian
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, United States.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Biological Sciences, Columbia University, New York, United States.|MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Miller
authors.affiliation: Department of Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States.
authors.forename: Susan
authors.identifier: 0000-0001-8714-7352
authors.initials: S
authors.lastname: Ferro-Novick
mesh_terms: D000071182:Autophagosomes / Q000378:metabolism*; D000071183:Autophagy-Related Proteins / Q000378:metabolism; D047389:Casein Kinase I / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D001678:Organelle Biogenesis; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: C434065:ATG9 protein, S cerevisiae; D000071183:Autophagy-Related Proteins; D008565:Membrane Proteins; C118289:SEC24 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D047389:Casein Kinase I; C070775:HRR25 protein, S cerevisiae
keywords: Autophagy; COPII vesicles; Hrr25; S. cerevisiae; Secretory pathway; cell biology