Role of the ENTH Domain in Phosphatidylinositol-4,5-Bisphosphate Binding and Endocytosis

DOI Web Site 被引用文献31件
  • Toshiki Itoh
    Department of Biochemistry, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
  • Seizo Koshiba
    RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama-shi, Kanagawa 230-0045, Japan.
  • Takanori Kigawa
    RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama-shi, Kanagawa 230-0045, Japan.
  • Akira Kikuchi
    Department of Biochemistry, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734–8551, Japan.
  • Shigeyuki Yokoyama
    RIKEN Genomic Sciences Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama-shi, Kanagawa 230-0045, Japan.
  • Tadaomi Takenawa
    Department of Biochemistry, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.

抄録

<jats:p> Endocytic proteins such as epsin, AP180, and Hip1R (Sla2p) share a conserved modular region termed the epsin NH <jats:sub>2</jats:sub> -terminal homology (ENTH) domain, which plays a crucial role in clathrin-mediated endocytosis through an unknown target. Here, we demonstrate a strong affinity of the ENTH domain for phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P <jats:sub>2</jats:sub> ]. With nuclear magnetic resonance analysis of the epsin ENTH domain, we determined that a cleft formed with positively charged residues contributed to phosphoinositide binding. Overexpression of a mutant, epsin Lys <jats:sup>76</jats:sup> → Ala <jats:sup>76</jats:sup> , with an ENTH domain defective in phosphoinositide binding, blocked epidermal growth factor internalization in COS-7 cells. Thus, interaction between the ENTH domain and PtdIns(4,5)P <jats:sub>2</jats:sub> is essential for endocytosis mediated by clathrin-coated pits. </jats:p>

収録刊行物

  • Science

    Science 291 (5506), 1047-1051, 2001-02-09

    American Association for the Advancement of Science (AAAS)

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