Role of Hrs in maturation of autophagosomes in mammalian cells.
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.
Tamai
Keiichi
K
Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Tanaka
Nobuyuki
N
Nara
Atsuki
A
Yamamoto
Akitsugu
A
Nakagawa
Ichiro
I
Yoshimori
Tamotsu
T
Ueno
Yoshiyuki
Y
Shimosegawa
Tooru
T
Sugamura
Kazuo
K
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
D015415:Biomarkers; D017931:DNA Primers; D056827:Endosomal Sorting Complexes Required for Transport; D010750:Phosphoproteins; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate