Unconventional secretion of Acb1 is mediated by autophagosomes.
Starving Dictyostelium discoideum cells secrete AcbA, an acyl coenzyme A-binding protein (ACBP) that lacks a conventional signal sequence for entering the endoplasmic reticulum (ER). Secretion of AcbA in D. discoideum requires the Golgi-associated protein GRASP. In this study, we report that starvation-induced secretion of Acb1, the Saccharomyces cerevisiae ACBP orthologue, also requires GRASP (Grh1). This highlights the conserved function of GRASP in unconventional secretion. Although genes required for ER to Golgi or Golgi to cell surface transport are not required for Acb1 secretion in yeast, this process involves autophagy genes and the plasma membrane t-SNARE, Sso1. Inhibiting transport to vacuoles does not affect Acb1 secretion. In sum, our experiments reveal a unique secretory pathway where autophagosomes containing Acb1 evade fusion with the vacuole to prevent cargo degradation. We propose that these autophagosome intermediates fuse with recycling endosomes instead to form multivesicular body carriers that then fuse with the plasma membrane to release cargo.
Center for Genomic Regulation, Barcelona 08003, Spain.
Juan M
JM
Duran
Christophe
C
Anjard
Chris
C
Stefan
William F
WF
Loomis
Vivek
V
Malhotra
D000595:Amino Acid Sequence; D001343:Autophagy / Q000235:genetics; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D005800:Genes, Fungal / Q000235:genetics; D006056:Golgi Apparatus / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D008561:Membrane Fusion; D008954:Models, Biological; D008969:Molecular Sequence Data; D057146:Multivesicular Bodies / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism*; D050765:Qa-SNARE Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D055571:Secretory Pathway; D014617:Vacuoles / Q000378:metabolism
C492820:ACB1 protein, S cerevisiae; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D050765:Qa-SNARE Proteins; C484455:SDF-2 protein, Dictyostelium discoideum; C084006:SSO1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins