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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1627-1635. Prepublished online as a Blood First Edition Paper on November 1, 2005; DOI 10.1182/blood-2005-03-1164. This Article Full Text Full Text (PDF) Supplemental Figures and Videos All Versions of this Article: 2005-03-1164v1 107/4/1627    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 Francis, S. A. Articles by Lerner, D. J. Search for Related Content PubMed PubMed Citation Articles by Francis, S. A. Articles by Lerner, D. J. Related Collections Phagocytes Cell Adhesion and Motility Cytoskeleton Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES Rho GEF Lsc is required for normal polarization, migration, and adhesion of formyl-peptide–stimulated neutrophils Sanjeev A. Francis, Xun Shen, Jeffrey B. Young, Prashant Kaul, and Daniel J. Lerner From the Department of Medicine, Weill Medical College of Cornell University, New York, NY. Neutrophil migration requires continuous reorganization of the cytoskeleton and cellular adhesion apparatus. Chemoattractants initiate intracellular signals that direct this reorganization. The signaling pathways that link chemoattractant receptors to the cytoskeleton and cellular adhesion apparatus are now being defined. Formyl-peptide chemoattractants released from bacteria stimulate G-protein–linked receptors on the surface of neutrophils and regulate the neutrophil cytoskeleton and adhesion apparatus through RhoA-dependent pathways. Lsc is a RhoA guanine nucleotide exchange factor that binds the heterotrimeric G-protein -subunits, G12 and G13. We have disrupted the Lsc gene and demonstrated that formyl-peptide–stimulated Lsc knock-out (KO) neutrophils are unable to generate and sustain a single-dominant pseudopod and migrate with increased speed and reduced directionality. Unexpectedly, we also found that Lsc is required for normal 2- and 1-integrin–dependent neutrophil adhesion. Lsc-deficient mice have a peripheral leukocytosis and extramedullary hematopoiesis, demonstrating that Lsc is required for leukocyte homeostasis. Lsc-deficient neutrophils are recruited normally to sites of bacterial peritonitis and chemical dermatitis, indicating that other signaling pathways compensate for the Lsc deficiency in some forms of inflammation. These results demonstrate that Lsc links formyl-peptide receptors to RhoA signaling pathways that regulate polarization, migration, and adhesion in neutrophils and that Lsc is required for leukocyte homeostasis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. V. Pajcini, J. H. Pomerantz, O. Alkan, R. Doyonnas, and H. M. Blau Myoblasts and macrophages share molecular components that contribute to cell-cell fusion J. Cell Biol., March 5, 2008; 180(5): 1005 - 1019. [Abstract] [Full Text] [PDF] R. S. Mishra, K. A. Carnevale, and M. K. Cathcart iPLA2{beta}: front and center in human monocyte chemotaxis to MCP-1 J. Exp. Med., February 18, 2008; 205(2): 347 - 359. [Abstract] [Full Text] [PDF] K. Wong, A. Van Keymeulen, and H. R. Bourne PDZRhoGEF and myosin II localize RhoA activity to the back of polarizing neutrophil-like cells J. Cell Biol., December 17, 2007; 179(6): 1141 - 1148. [Abstract] [Full Text] [PDF] A. D. Dubash, K. Wennerberg, R. Garcia-Mata, M. M. Menold, W. T. Arthur, and K. Burridge A novel role for Lsc/p115 RhoGEF and LARG in regulating RhoA activity downstream of adhesion to fibronectin J. Cell Sci., November 15, 2007; 120(22): 3989 - 3998. [Abstract] [Full Text] [PDF] J. P. Brown, C. Taube, N. Miyahara, T. Koya, R. Pelanda, E. W. Gelfand, and R. M. Torres Arhgef1 Is Required by T Cells for the Development of Airway Hyperreactivity and Inflammation Am. J. Respir. Crit. Care Med., July 1, 2007; 176(1): 10 - 19. [Abstract] [Full Text] [PDF] Z. Liao, C. I. Seye, G. A. Weisman, and L. Erb The P2Y2 nucleotide receptor requires interaction with {alpha}v integrins to access and activate G12 J. Cell Sci., May 1, 2007; 120(9): 1654 - 1662. [Abstract] [Full Text] [PDF] S. Rieken, A. Sassmann, S. Herroeder, B. Wallenwein, A. Moers, S. Offermanns, and N. Wettschureck G12/G13 family g proteins regulate marginal zone B cell maturation, migration, and polarization. J. Immunol., September 1, 2006; 177(5): 2985 - 2993. [Abstract] [Full Text] [PDF] T. K. Roepke, A. Anantharam, P. Kirchhoff, S. M. Busque, J. B. Young, J. P. Geibel, D. J. Lerner, and G. W. Abbott The KCNE2 Potassium Channel Ancillary Subunit Is Essential for Gastric Acid Secretion J. Biol. Chem., August 18, 2006; 281(33): 23740 - 23747. [Abstract] [Full Text] [PDF]

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