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Blood, 1 December 2004, Vol. 104, No. 12, pp. 3758-3765. Prepublished online as a Blood First Edition Paper on August 12, 2004; DOI 10.1182/blood-2004-03-0781. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-0781v1 104/12/3758    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sun, C. X. Articles by Glogauer, M. Search for Related Content PubMed PubMed Citation Articles by Sun, C. X. Articles by Glogauer, M. Related Collections Phagocytes Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES Rac1 is the small GTPase responsible for regulating the neutrophil chemotaxis compass Chun Xiang Sun, Gregory P. Downey, Fei Zhu, Adeline L. Y. Koh, Herman Thang, and Michael Glogauer From the Faculty of Dentistry, University of Toronto; and the Division of Respirology, Department of Medicine, University of Toronto and Toronto General Hospital Research Institute of the University Health Network, ON, Canada. Although both of the small Rho guanosine triphosphatases (GTPases) Rac1 and Rac2 have been demonstrated to play a role in chemotaxis, the precise and possible unique roles performed by each of these 2 Rac isoforms in neutrophil chemotaxis have not been defined. To elucidate the specific roles of Rac1 and Rac2 in neutrophils during the process of chemotaxis, we generated mice deficient in Rac1, Rac2, or in both Rac1 and Rac2 in cells of myeloid lineage including neutrophils by mating Rac2 null mice with mice carrying a conditional allele for Rac1 and expressing the Cre recombinase downstream of a specific myeloid promoter, lysozyme M. We demonstrate here that although Rac1 null neutrophils display normal chemokinesis, they are unable to migrate toward the source of the chemoattractant. By contrast, Rac2 null neutrophils can orient toward the chemoattractant source but are unable to migrate efficiently. We show that Rac1 is essential for gradient detection and orientation toward the chemoattractant source through spatially constrained regulation of phosphoinositol-3,4,5-trisphosphate (PIP3) and Akt in the leading edge and confirm that Rac2 is the primary regulator of actin assembly providing the molecular motor for neutrophil translocation during chemotaxis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Mehta, M. Glogauer, S. Becart, A. Altman, and K. M. Coggeshall Adaptor Protein SLAT Modulates Fc{gamma} Receptor-mediated Phagocytosis in Murine Macrophages J. Biol. Chem., May 1, 2009; 284(18): 11882 - 11891. [Abstract] [Full Text] [PDF] S. Liu, M. Kapoor, and A. Leask Rac1 Expression by Fibroblasts Is Required for Tissue Repair in Vivo Am. J. Pathol., May 1, 2009; 174(5): 1847 - 1856. [Abstract] [Full Text] [PDF] A. Utomo, J. Hirahashi, D. Mekala, K. Asano, M. Glogauer, X. Cullere, and T. N. 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Ellen, and M. Glogauer Expression and translocation of fluorescent-tagged p21-activated kinase-binding domain and PH domain of protein kinase B during murine neutrophil chemotaxis J. Leukoc. Biol., September 1, 2007; 82(3): 559 - 566. [Abstract] [Full Text] [PDF] J. Gomez-Cambronero, M. Di Fulvio, and K. Knapek Understanding phospholipase D (PLD) using leukocytes: PLD involvement in cell adhesion and chemotaxis J. Leukoc. Biol., August 1, 2007; 82(2): 272 - 281. [Abstract] [Full Text] [PDF] F. Asperti-Boursin, E. Real, G. Bismuth, A. Trautmann, and E. Donnadieu CCR7 ligands control basal T cell motility within lymph node slices in a phosphoinositide 3-kinase- independent manner J. Exp. Med., May 14, 2007; 204(5): 1167 - 1179. [Abstract] [Full Text] [PDF] M.-D. Filippi, K. Szczur, C. E. Harris, and P.-Y. Berclaz Rho GTPase Rac1 is critical for neutrophil migration into the lung Blood, February 1, 2007; 109(3): 1257 - 1264. [Abstract] [Full Text] [PDF] K. Szczur, H. Xu, S. Atkinson, Y. 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Sanematsu, T. Sasazuki, T. Sasaki, et al. DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis J. Cell Biol., August 28, 2006; 174(5): 647 - 652. [Abstract] [Full Text] [PDF] A. P. Wheeler, C. M. Wells, S. D. Smith, F. M. Vega, R. B. Henderson, V. L. Tybulewicz, and A. J. Ridley Rac1 and Rac2 regulate macrophage morphology but are not essential for migration J. Cell Sci., July 1, 2006; 119(13): 2749 - 2757. [Abstract] [Full Text] [PDF] E. Vachon, R. Martin, J. Plumb, V. Kwok, R. W. Vandivier, M. Glogauer, A. Kapus, X. Wang, C.-W. Chow, S. Grinstein, et al. CD44 is a phagocytic receptor Blood, May 15, 2006; 107(10): 4149 - 4158. [Abstract] [Full Text] [PDF] L. Vidali, F. Chen, G. Cicchetti, Y. Ohta, and D. J. Kwiatkowski Rac1-null Mouse Embryonic Fibroblasts Are Motile and Respond to Platelet-derived Growth Factor Mol. Biol. Cell, May 1, 2006; 17(5): 2377 - 2390. [Abstract] [Full Text] [PDF] S. A. Francis, X. Shen, J. B. Young, P. Kaul, and D. J. 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