1. Academic Validation
  2. A Tecpr1-dependent selective autophagy pathway targets bacterial pathogens

A Tecpr1-dependent selective autophagy pathway targets bacterial pathogens

  • Cell Host Microbe. 2011 May 19;9(5):376-89. doi: 10.1016/j.chom.2011.04.010.
Michinaga Ogawa 1 Yuko Yoshikawa Taira Kobayashi Hitomi Mimuro Makoto Fukumatsu Kotaro Kiga Zhenzi Piao Hiroshi Ashida Mitsutaka Yoshida Shigeru Kakuta Tomohiro Koyama Yoshiyuki Goto Takahiro Nagatake Shinya Nagai Hiroshi Kiyono Magdalena Kawalec Jean-Marc Reichhart Chihiro Sasakawa
Affiliations

Affiliation

  • 1 Division of Bacterial Infection, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. ogacho@ims.u-tokyo.ac.jp
Abstract

Selective Autophagy of Bacterial pathogens represents a host innate immune mechanism. Selective Autophagy has been characterized on the basis of distinct cargo receptors but the mechanisms by which different cargo receptors are targeted for autophagic degradation remain unclear. In this study we identified a highly conserved Tectonin domain-containing protein, Tecpr1, as an Atg5 binding partner that colocalized with Atg5 at Shigella-containing phagophores. Tecpr1 activity is necessary for efficient autophagic targeting of bacteria, but has no effect on rapamycin- or starvation-induced canonical Autophagy. Tecpr1 interacts with WIPI-2, a yeast Atg18 homolog and PI(3)P-interacting protein required for phagophore formation, and they colocalize to phagophores. Although Tecpr1-deficient mice appear normal, Tecpr1-deficient MEFs were defective for selective Autophagy and supported increased intracellular multiplication of Shigella. Further, depolarized mitochondria and misfolded protein aggregates accumulated in the Tecpr1-knockout MEFs. Thus, we identify a Tecpr1-dependent pathway as important in targeting Bacterial pathogens for selective Autophagy.

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