Isoform-specific membrane targeting mechanism of Rac during FcγR-mediated phagocytosis: Positive charge-dependent and independent targeting mechanism of Rac to the phagosome

Takehiko Ueyama, Mika Eto, Keiichiro Kami, Toshihiko Tatsuno, Toshihiro Kobayashi, Yasuhito Shirai, Michelle R. Lennartz, Ryu Takeya, Hideki Sumimoto, Naoaki Saito

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Rac1 and Rac2 are capable of stimulating superoxide production in vitro, but their targeting and functional mechanisms are still unknown. In the present study, we found that Rac1, 2, and 3 all accumulate at the phagosome during FcγR-mediated phagocytosis, and that the order of accumulation (Rac1 > Rac3 > Rac2) depends on the net positive charge in their polybasic (PB) regions (183-188 aa). Although all GFP-tagged prenylated PB regions of Rac isoforms (GFP-Rac(PB)) and GFP-tagged prenylated 6 Ala (GFP-6A) accumulated during phagocytosis, GFP-Rac2(PB) and GFP-6A showed weak accumulation at the phagosome through a linear structure connecting the phagosome and endomembranes. The PB region of Rac1 showed strong phospholipid interaction with PI(3)P, PI(4)P, PI(5)P, PI(3,4,5)P3, and phosphatidic acid, however, that of Rac1 did not. Constitutively active Rac2, GFP-Rac2(Q61L), was predominantly localized at the endomembranes; these endomembranes fused to the phagosome through the linear structure during phagocytosis, and this accumulation mechanism did not depend on positive charge in the PB region. Our conclusion is that Rac1 directly targets to the phagosome using the positively charged PB region and this accumulation mechanism is likely enhanced by the phospholipids. In addition to this mechanism, Rac2 has a positive charge-independent mechanism in which Rac2 initially targets to endomembranes and then these endomembranes fuse to the phagosome.

Original languageEnglish
Pages (from-to)2381-2390
Number of pages10
JournalJournal of Immunology
Volume175
Issue number4
DOIs
Publication statusPublished - Aug 15 2005

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Isoform-specific membrane targeting mechanism of Rac during FcγR-mediated phagocytosis: Positive charge-dependent and independent targeting mechanism of Rac to the phagosome'. Together they form a unique fingerprint.

  • Cite this