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

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

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)387-394
Number of pages8
JournalJournal of Biochemistry
Volume145
Issue number3
DOIs
Publication statusPublished - 2009 Mar 1
Externally publishedYes

Keywords

  • Apoptosis
  • Phagocytosis
  • Phosphatidylserine
  • Scavenger receptor
  • Small G protein

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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