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


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.

SUBMITTER: Kunisaki Y 

PROVIDER: S-EPMC2064308 | biostudies-literature | 2006 Aug

REPOSITORIES: biostudies-literature

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

Kunisaki Yuya Y   Nishikimi Akihiko A   Tanaka Yoshihiko Y   Takii Ryosuke R   Noda Mayuko M   Inayoshi Ayumi A   Watanabe Ken-ichi K   Sanematsu Fumiyuki F   Sasazuki Takehiko T   Sasaki Takehiko T   Fukui Yoshinori Y  

The Journal of cell biology 20060801 5


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 mov  ...[more]

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