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A Tecpr1-dependent selective autophagy pathway targets bacterial pathogens

Michinaga Ogawa1, Yuko Yoshikawa1, Taira Kobayashi1, Hitomi Mimuro1, Makoto Fukumatsu1, Kotaro Kiga1, Zhenzi Piao1, Hiroshi Ashida1, Mitsutaka Yoshida2, Shigeru Kakuta3,*, Tomohiro Koyama4, Yoshiyuki Goto5, Takahiro Nagatake5, Shinya Nagai4, Hiroshi Kiyono5, Magdalena Kawalec6, Jean-Marc Reichhart6 and Chihiro Sasakawa1, 7
1Division of Bacterial Infection, 5Division of Mucosal Immunology, Department of Microbiology and Immunology, 3Center for Experimental Medicine and Systems Biology, Institute of Medical Science, The University of Toky, 2Division of Ultrastructural Research, BioMedical Research Center, Graduate School of Medicine, Juntendo University, 4Nippon Institute for Biological Science, 6IUF-UdS, IBMC UPR 9022 CNRS, 7Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo

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.