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The leading edge of a migrating cell is built up via one or more positive feedback loops. Kunisaki et al. (page 647) present evidence for a feedback loop that is required for the greater localization, although not greater overall abundance, of the critical migration mediator phosphatidylinositol 3,4,5-triphosphate (PIP₃). The loop is driven by the newly identified Rac activator DOCK2.

Kunisaki et al. had earlier identified DOCK2 as a regulator of lymphocyte migration. They now find that DOCK2 is also required for directed migration in neutrophils. DOCK2-deficient neutrophils migrated at almost half the speed of wild-type cells, and wandered rather than taking a straight path toward a chemoattractant. The leading edge in these cells was not as stable as that found in wild-type neutrophils.

In the presence of chemoattractant, DOCK2 translocated to the neutrophil leading edge in a PI3K-dependent manner. Its presence there was necessary for the full activation of Rac (which drives actin polymerization) and accumulation of PIP₃. Cells lacking DOCK2 still activated PI3K and thus produced high levels of PIP₃, but without DOCK2 the PIP₃ did not find its way to the leading edge.

A positive feedback loop is believed to maintain high PIP₃ levels and Rac activity at the leading edge. The new results suggest that this loop regulates the localization of PIP₃, not the activity of the PI3K that generates the PIP₃.

Rabiya S. Tuma

rabiya{at}nasw.org

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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, and Yoshinori Fukui
J. Cell Biol. 2006 174: 647-652. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 1340K) Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tuma, R. S. Search for Related Content PubMed Articles by Tuma, R. S. Related Collections Related Article Social Bookmarking                      What's this?