title: Rab39a interacts with phosphatidylinositol 3-kinase and negatively regulates autophagy induced by lipopolysaccharide stimulation in macrophages.
abstract: Rab39a has pleiotropic functions in phagosome maturation, inflammatory activation and neuritogenesis. Here, we characterized Rab39a function in membrane trafficking of phagocytosis and autophagy induction in macrophages. Rab39a localized to the periphery of LAMP2-positive vesicles and showed the similar kinetics on the phagosome to that of LAMP1. The depletion of Rab39a did not influence the localization of LAMP2 to the phagosome, but it augments the autophagosome formation and LC3 processing by lipopolysaccharide (LPS) stimulation. The augmentation of autophagosome formation in Rab39a-knockdown macrophages was suppressed by Atg5 depletion or an inhibitor for phosphatidylinostol 3-kinase (PI3K). Immunoprecipitation analysis revealed that Rab39a interacts with PI3K and that the amino acid residues from 34(th) to 41(st) in Rab39a were indispensable for this interaction. These results suggest that Rab39a negatively regulates the LPS-induced autophagy in macrophages.
authors.affiliation: Department of Infectious Diseases, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Seto
authors.affiliation: Department of Health Science, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Sugaya
authors.affiliation: Department of Infectious Diseases, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Tsujimura
authors.affiliation: Department of Health Science, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Toshi
authors.initials: T
authors.lastname: Nagata
authors.affiliation: Department of Infectious Diseases, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Horii
authors.affiliation: Department of Infectious Diseases, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan ; Executive Director, Hamamatsu University School of Medicine, Hamamatsu Hamamatsu, Shizuoka, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Koide
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D008070:Lipopolysaccharides; D051907:Lysosomal Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D020691:rab GTP-Binding Proteins; C052255:Lamp1 protein, mouse; D052118:Lysosomal-Associated Membrane Protein 1; C583043:Rab39A protein, mouse