DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis

Yuya Kunisaki, Akihiko Nishikimi, Yoshihiko Tanaka, Ryosuke Takii, Mayuko Noda, Ayumi Inayoshi, Ken Ichi Watanabe, Fumiyuki Sanematsu, Takehiko Sasazuki, Takehiko Sasaki, Yoshinori Fukui

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146 Citations (Scopus)

Abstract

Neutrophils are highly motile leukocytes, and they play important roles in the innate immune response to invading pathogens. Neutrophil chemotaxis requires Rac activation, yet the Rac activators functioning downstream of chemoattractant receptors remain to be determined. We show that DOCK2, which is a mammalian homologue of Caenorhabditis elegans CED-5 and Drosophila melanogaster Myoblast City, regulates motility and polarity during neutrophil chemotaxis. Although DOCK2-deficient neutrophils moved toward the chemoattractant source, they exhibited abnormal migratory behavior with a marked reduction in translocation speed. In DOCK2-deficient neutrophils, chemoattractant-induced activation of both Rac1 and Rac2 were severely impaired, resulting in the loss of polarized accumulation of F-actin and phosphatidylinositol 3,4,5-triphosphate (PIP3) at the leading edge. On the other hand, we found that DOCK2 associates with PIP3 and translocates to the leading edge of chemotaxing neutrophils in a phosphatidylinositol 3-kinase (PI3K)- dependent manner. These results indicate that during neutrophil chemotaxis DOCK2 regulates leading edge formation through PIP3-dependent membrane translocation and Rac activation.

Original languageEnglish
Pages (from-to)647-652
Number of pages6
JournalJournal of Cell Biology
Volume174
Issue number5
DOIs
Publication statusPublished - Aug 28 2006

All Science Journal Classification (ASJC) codes

  • Cell Biology

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    Kunisaki, Y., Nishikimi, A., Tanaka, Y., Takii, R., Noda, M., Inayoshi, A., Watanabe, K. I., Sanematsu, F., Sasazuki, T., Sasaki, T., & Fukui, Y. (2006). DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis. Journal of Cell Biology, 174(5), 647-652. https://doi.org/10.1083/jcb.200602142