Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. Signal., 21 April 2009
Vol. 2, Issue 67, p. ec142
[DOI: 10.1126/scisignal.267ec142]


Chemotaxis Nuts and Bolts of Chemotaxis

Stella M. Hurtley

Science, AAAS, Cambridge CB2 1LQ, UK

During chemotaxis, the small GTPase Rac is locally activated to extend membrane protrusions in the direction of migration. This localized Rac activation is achieved, at least in part, by focusing Rac GEFs (guanine nucleotide exchange factors) at the leading edge of the cell, yet the mechanism controlling subcellular localization of Rac GEFs is poorly understood. DOCK2 is a Rac GEF that regulates motility and polarity during neutrophil chemotaxis. Nishikimi et al. (see the Perspective by Côté and Vuori) provide evidence that intracellular DOCK2 dynamics are sequentially regulated by two distinct phospholipids. In response to chemoattractants, DOCK2 rapidly translocates to the plasma membrane of chemotaxing neutrophils. This initial translocation is mediated by phosphatidylinositol 3,4,5-trisphosphate (PIP3), whereas subsequent accumulation of DOCK2 at the leading edge requires de novo synthesis of phosphatidic acid (PA). PA focuses DOCK2 localization through direct binding to DOCK2’s C-terminal polybasic clusters, resulting in local induction of actin polymerization. When this interaction is blocked, neutrophils fail to form leading edges properly and exhibit defects in chemotaxis. Thus, PA is critical for leading edge formation and stabilization during chemotaxis.

A. Nishikimi, H. Fukuhara, W. Su, T. Hongu, S. Takasuga, H. Mihara, Q. Cao, F. Sanematsu, M. Kanai, H. Hasegawa, Y. Tanaka, M. Shibasaki, Y. Kanaho, T. Sasaki, M. A. Frohman, Y. Fukui, Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis. Science 324, 384–387 (2009). [Abstract] [Full Text]

J.-F. Côté, K. Vuori, Two lipids that give direction. Science 324, 346–347 (2009). [Summary] [Full Text]

Citation: S. M. Hurtley, Nuts and Bolts of Chemotaxis. Sci. Signal. 2, ec142 (2009).

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882