Signalling pathway involving GULP, MAPK and Rac1 for SR-BI-induced phagocytosis of apoptotic cells.

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概要

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• Class B scavenger receptor type I (SR-BI) is a phosphatidylserine (PS)-recognizing receptor of testicular Sertoli cells responsible for the phagocytosis of spermatogenic cells undergoing apoptosis. Here, we determined signal mediators that compose a signalling pathway for SR-BI-induced phagocytosis. Results of a yeast two-hybrid analysis and a cell-free binding assay indicated that SR-BI binds to engulfment adapter protein (GULP) using the C-terminal intracellular domain. A co-immunoprecipitation analysis showed the existence of a complex of GULP and SR-BI in cells prior to the activation of SR-BI by PS. A reduction of GULP expression in phagocytes decreased the SR-BI-mediated phagocytosis of apoptotic cells. Administration to phagocytes of PS-containing liposomes increased the levels of the GTP-bound form of Rac1 and the phosphorylated forms of mitogen-activated protein kinases (MAPK) p38 and extracellular signal-related kinase 1 and 2. Finally, lowering the expression of GULP abrogated MAPK phosphorylation, and the presence of MAPK inhibitors reduced the level of GTP-bound Rac1 in PS-activated phagocytes. These results collectively suggested the following signalling pathway for the SR-BI-induced phagocytosis: (i) PS-recognizing SR-BI activates associated GULP; (ii) activated GULP induces MAPK phosphorylation; (iii) activated MAPK increases GTP-bound Rac1; and (iv) activated Rac1 induces a rearrangement of the actin cytoskeleton.

• 日本生化学会 = Japanese Biochemical Societyの論文
• 2009-03-01

著者

• Shiratsuchi Akiko

  Graduate School Of Medical Science Kanazawa University

• Nakanishi Yoshinobu

  Graduate School Of Medical Science Kanazawa University

• Kim In-san

  Cell And Matrix Research Institute School Of Medicine Kyungpook National University

• OSADA Yoichi

  Graduate School of Medical Science, Kanazawa University

• SUNATANI Toshiro

  Graduate School of Medical Science, Kanazawa University

• Osada Yoichi

  Graduate School Of Medical Science Kanazawa University

• Sunatani Toshiro

  Graduate School Of Medical Science Kanazawa University

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