title: Role of Hrs in maturation of autophagosomes in mammalian cells.
abstract: Autophagy is an evolutionarily conserved system responsible for the degradation of cellular components and contributes to the increasing of amino acid pool, organelle turnover, and elimination of intracellular bacteria. The molecular process of autophagy is still unclear. Here we demonstrate that Hrs, a master regulator in endosomal protein sorting, plays critical roles for the autophagic degradation of non-specific proteins and Streptococcus pyogenes. We found that Hrs containing FYVE domain is localized to autophagosomes. Hrs depletion resulted in a significant decrease in the number of mature autophagosomes (autophagolysosomes) detected by the co-localization of autophagosome marker LC3 and lysosome marker LAMP-1. In contrast, formation of the primary autophagosome, detected by LC3 immunoblotting and lysosomal degradation of non-specific proteins, were not significantly altered by Hrs depletion. Based on these results, we propose a novel function of Hrs, as a crucial player in the maturation of autophagosomes.
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tamai
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Atsuki
authors.initials: A
authors.lastname: Nara
authors.forename: Akitsugu
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakagawa
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Yoshimori
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ueno
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sugamura
mesh_terms: D001343:Autophagy / Q000502:physiology*; D001483:Base Sequence; D015415:Biomarkers; D017931:DNA Primers; D056827:Endosomal Sorting Complexes Required for Transport; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D008247:Lysosomes / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D034622:RNA Interference
chemical_list: D015415:Biomarkers; D017931:DNA Primers; D056827:Endosomal Sorting Complexes Required for Transport; D010750:Phosphoproteins; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate