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

フォーマット:

論文

責任表示:

Osada, Yoichi ; Sunatani, Toshiro ; Kim, In-San ; Nakanishi, Yoshinobu ; Shiratsuchi, Akiko

言語:

英語

出版情報:

日本生化学会 = Japanese Biochemical Society, 2009-03-01

著者名:

• Osada, Yoichi
• Sunatani, Toshiro
• Kim, In-San
• Nakanishi, Yoshinobu
• Shiratsuchi, Akiko

掲載情報:

Journal of biochemistry

ISSN:

1756-2651      

巻:

145

通号:

3

開始ページ:

387

終了ページ:

394

バージョン:

publisher

概要:

金沢大学医薬保健研究域薬学系<br />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 determi … ned 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. 続きを見る

URL:

http://hdl.handle.net/2297/18196