title: A Tecpr1-dependent selective autophagy pathway targets bacterial pathogens.
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.
authors.affiliation: Division of Bacterial Infection, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. ogacho@ims.u-tokyo.ac.jp
authors.forename: Michinaga
authors.initials: M
authors.lastname: Ogawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Taira
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Hitomi
authors.initials: H
authors.lastname: Mimuro
authors.forename: Makoto
authors.initials: M
authors.lastname: Fukumatsu
authors.forename: Kotaro
authors.initials: K
authors.lastname: Kiga
authors.forename: Zhenzi
authors.initials: Z
authors.lastname: Piao
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ashida
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Yoshida
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kakuta
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Koyama
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Goto
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nagatake
authors.forename: Shinya
authors.initials: S
authors.lastname: Nagai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kawalec
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Reichhart
authors.forename: Chihiro
authors.initials: C
authors.lastname: Sasakawa
mesh_terms: D000818:Animals; D001343:Autophagy; D000071187:Autophagy-Related Protein 5; D002478:Cells, Cultured; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008954:Models, Biological; D010588:Phagosomes / Q000276:immunology; D025941:Protein Interaction Mapping; D012760:Shigella / Q000276:immunology*; D020798:Two-Hybrid System Techniques
chemical_list: C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C560616:Tecpr1 protein, mouse