HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 7, 6087-6097, February 13, 2004

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 279/7/6087    most recent M307087200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Grimsley, C. M. Articles by Ravichandran, K. S. Search for Related Content PubMed PubMed Citation Articles by Grimsley, C. M. Articles by Ravichandran, K. S. Social Bookmarking                      What's this?

Dock180 and ELMO1 Proteins Cooperate to Promote Evolutionarily Conserved Rac-dependent Cell Migration^*

Cynthia M. Grimsley¶, Jason M. Kinchen||**, Annie-Carole Tosello-Trampont, Enrico Brugnera, Lisa B. Haney, Mingjian Lu, Qi Chen, Doris Klingele**, Michael O. Hengartner**, and Kodi S. Ravichandran

From the Beirne Carter Center for Immunology Research and the Department of Microbiology and Pharmacology, University of Virginia, Charlottesville, Virginia 22908, ^||Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook, New York 11743, ^**Institute of Molecular Biology, University of Zürich, Zürich 8057, Switzerland, and Cellular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037

Cell migration is essential throughout embryonic and adult life. In numerous cell systems, the small GTPase Rac is required for lamellipodia formation at the leading edge and movement ability. However, the molecular mechanisms leading to Rac activation during migration are still unclear. Recently, a mammalian superfamily of proteins related to the prototype member Dock180 has been identified with homologues in Drosophila and Caenorhabditis elegans. Here, we addressed the role of Dock180 and ELMO1 proteins, which function as a complex to mediate Rac activation, in mammalian cell migration. Using mutants of Dock180 and ELMO1 in a Transwell assay as well as transgenic rescue of a C. elegans mutant lacking CED-5 (Dock180 homologue), we identified specific regions of Dock180 and ELMO1 required for migration in vitro and in a whole animal model. In both systems, the Dock180·ELMO1 complex formation and the ability to activate Rac were required. We also found that ELMO1 regulated multiple Dock180 superfamily members to promote migration. Interestingly, deletion mutants of ELMO1 missing their first 531 or first 330 amino acids that can still bind and cooperate with Dock180 in Rac activation failed to promote migration, which correlated with the inability to localize to lamellipodia. This finding suggests that Rac activation by the ELMO·Dock180 complex at discrete intracellular locations mediated by the N-terminal 330 amino acids of ELMO1 rather than generalized Rac activation plays a role in cell migration.

Received for publication, July 2, 2003 , and in revised form, November 19, 2003.

^* This work was supported by a grant from the NIGMS, National Institutes of Health (to K. S. R.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains Supplemental Figs. 1 and 2.

^¶ Supported by an infectious disease training grant from the National Institutes of Health.

To whom correspondence should be addressed: Carter Immunology Center, University of Virginia, MR4, Rm. 4072D, Box 801386, Lane Rd., Charlottesville, Virginia 22908, Tel.: 434-243-6093; Fax: 434-924-1221; E-mail: Ravi{at}virginia.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. Ho, T. Irvine, G. J.A. Vilk, G. Lajoie, K. S. Ravichandran, S. J.A. D'Souza, and L. Dagnino Integrin-linked Kinase Interactions with ELMO2 Modulate Cell Polarity Mol. Biol. Cell, July 1, 2009; 20(13): 3033 - 3043. [Abstract] [Full Text] [PDF]

				K. R. Legate, S. A. Wickstrom, and R. Fassler Genetic and cell biological analysis of integrin outside-in signaling Genes & Dev., February 15, 2009; 23(4): 397 - 418. [Abstract] [Full Text] [PDF]

				Q. Chen, C. A. Peto, G. D. Shelton, A. Mizisin, P. E. Sawchenko, and D. Schubert Loss of Modifier of Cell Adhesion Reveals a Pathway Leading to Axonal Degeneration J. Neurosci., January 7, 2009; 29(1): 118 - 130. [Abstract] [Full Text] [PDF]

				A. Para, M. Krischke, S. Merlot, Z. Shen, M. Oberholzer, S. Lee, S. Briggs, and R. A. Firtel Dictyostelium Dock180-related RacGEFs Regulate the Actin Cytoskeleton during Cell Motility Mol. Biol. Cell, January 1, 2009; 20(2): 699 - 707. [Abstract] [Full Text] [PDF]

				D. Komander, M. Patel, M. Laurin, N. Fradet, A. Pelletier, D. Barford, and J.-F. Cote An {alpha}-Helical Extension of the ELMO1 Pleckstrin Homology Domain Mediates Direct Interaction to DOCK180 and Is Critical in Rac Signaling Mol. Biol. Cell, November 1, 2008; 19(11): 4837 - 4851. [Abstract] [Full Text] [PDF]

				M. Laurin, N. Fradet, A. Blangy, A. Hall, K. Vuori, and J.-F. Cote The atypical Rac activator Dock180 (Dock1) regulates myoblast fusion in vivo PNAS, October 7, 2008; 105(40): 15446 - 15451. [Abstract] [Full Text] [PDF]

				J. Sai, D. Raman, Y. Liu, J. Wikswo, and A. Richmond Parallel Phosphatidylinositol 3-Kinase (PI3K)-dependent and Src-dependent Pathways Lead to CXCL8-mediated Rac2 Activation and Chemotaxis J. Biol. Chem., September 26, 2008; 283(39): 26538 - 26547. [Abstract] [Full Text] [PDF]

				Y. Q. Xiao, C. G. Freire-de-Lima, W. P. Schiemann, D. L. Bratton, R. W. Vandivier, and P. M. Henson Transcriptional and Translational Regulation of TGF-{beta} Production in Response to Apoptotic Cells J. Immunol., September 1, 2008; 181(5): 3575 - 3585. [Abstract] [Full Text] [PDF]

				N. O. Deakin and C. E. Turner Paxillin comes of age J. Cell Sci., August 1, 2008; 121(15): 2435 - 2444. [Abstract] [Full Text] [PDF]

				S. Rauch, K. Pulkkinen, K. Saksela, and O. T. Fackler Human Immunodeficiency Virus Type 1 Nef Recruits the Guanine Exchange Factor Vav1 via an Unexpected Interface into Plasma Membrane Microdomains for Association with p21-Activated Kinase 2 Activity J. Virol., March 15, 2008; 82(6): 2918 - 2929. [Abstract] [Full Text] [PDF]

				R. D'Angelo, S. Aresta, A. Blangy, L. Del Maestro, D. Louvard, and M. Arpin Interaction of Ezrin with the Novel Guanine Nucleotide Exchange Factor PLEKHG6 Promotes RhoG-dependent Apical Cytoskeleton Rearrangements in Epithelial Cells Mol. Biol. Cell, December 1, 2007; 18(12): 4780 - 4793. [Abstract] [Full Text] [PDF]

				M. J. Jarzynka, B. Hu, K.-M. Hui, I. Bar-Joseph, W. Gu, T. Hirose, L. B. Haney, K. S. Ravichandran, R. Nishikawa, and S.-Y. Cheng ELMO1 and Dock180, a Bipartite Rac1 Guanine Nucleotide Exchange Factor, Promote Human Glioma Cell Invasion Cancer Res., August 1, 2007; 67(15): 7203 - 7211. [Abstract] [Full Text] [PDF]

				J. M. Kinchen and K. S. Ravichandran Journey to the grave: signaling events regulating removal of apoptotic cells J. Cell Sci., July 1, 2007; 120(13): 2143 - 2149. [Abstract] [Full Text] [PDF]

				L. Balagopalan, M.-H. Chen, E. R. Geisbrecht, and S. M. Abmayr The CDM Superfamily Protein MBC Directs Myoblast Fusion through a Mechanism That Requires Phosphatidylinositol 3,4,5-Triphosphate Binding but Is Independent of Direct Interaction with DCrk Mol. Cell. Biol., December 15, 2006; 26(24): 9442 - 9455. [Abstract] [Full Text] [PDF]

				K. Agopian, B. L. Wei, J. V. Garcia, and D. Gabuzda A Hydrophobic Binding Surface on the Human Immunodeficiency Virus Type 1 Nef Core Is Critical for Association with p21-Activated Kinase 2 J. Virol., March 15, 2006; 80(6): 3050 - 3061. [Abstract] [Full Text] [PDF]

				C. M. Grimsley, M. Lu, L. B. Haney, J. M. Kinchen, and K. S. Ravichandran Characterization of a Novel Interaction between ELMO1 and ERM Proteins J. Biol. Chem., March 3, 2006; 281(9): 5928 - 5937. [Abstract] [Full Text] [PDF]

				Y. Makino, M. Tsuda, S. Ichihara, T. Watanabe, M. Sakai, H. Sawa, K. Nagashima, S. Hatakeyama, and S. Tanaka Elmo1 inhibits ubiquitylation of Dock180. J. Cell Sci., March 1, 2006; 119(Pt 5): 923 - 932. [Abstract] [Full Text] [PDF]

				F. Edwin, R. Singh, R. Endersby, S. J. Baker, and T. B. Patel The Tumor Suppressor PTEN Is Necessary for Human Sprouty 2-mediated Inhibition of Cell Proliferation J. Biol. Chem., February 24, 2006; 281(8): 4816 - 4822. [Abstract] [Full Text] [PDF]

				H. Katoh, K. Hiramoto, and M. Negishi Activation of Rac1 by RhoG regulates cell migration J. Cell Sci., January 1, 2006; 119(1): 56 - 65. [Abstract] [Full Text] [PDF]

				N. Meller, S. Merlot, and C. Guda CZH proteins: a new family of Rho-GEFs J. Cell Sci., November 1, 2005; 118(21): 4937 - 4946. [Abstract] [Full Text] [PDF]

				R. Zaidel-Bar, Z. Kam, and B. Geiger Polarized downregulation of the paxillin-p130CAS-Rac1 pathway induced by shear flow J. Cell Sci., September 1, 2005; 118(17): 3997 - 4007. [Abstract] [Full Text] [PDF]

				Q. Chen, T.-J. Chen, P. C. Letourneau, L. Da F. Costa, and D. Schubert Modifier of Cell Adhesion Regulates N-Cadherin-Mediated Cell-Cell Adhesion and Neurite Outgrowth J. Neurosci., January 12, 2005; 25(2): 281 - 290. [Abstract] [Full Text] [PDF]