Role of Hrs in maturation of autophagosomes in mammalian cells

Keiichi Tamai, Nobuyuki Tanaka, Atsuki Nara, Akitsugu Yamamoto, Ichiro Nakagawa, Tamotsu Yoshimori, Yoshiyuki Ueno, Tooru Shimosegawa, Kazuo Sugamura

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)721-727
Number of pages7
JournalBiochemical and biophysical research communications
Volume360
Issue number4
DOIs
Publication statusPublished - 2007 Sep 7
Externally publishedYes

Keywords

  • Autophagy
  • FYVE domain
  • LC3
  • Streptococci

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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