Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 5582K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by van Buul, J. D. Articles by Burridge, K. Search for Related Content PubMed PubMed Citation Articles by van Buul, J. D. Articles by Burridge, K. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Substance via MeSH Related Collections Related Article Social Bookmarking                            What's this?

RhoG regulates endothelial apical cup assembly downstream from ICAM1 engagement and is involved in leukocyte trans-endothelial migration

¹ Department of Cell and Developmental Biology and ² Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599
³ Cardiovascular Research Center and ⁴ Department of Microbiology, Mellon Prostate Cancer Institute, University of Virginia, Charlottesville, VA 22908

Correspondence to Jaap D. van Buul: j.vanbuul{at}sanquin.nl; or Keith Burridge: keith_burridge{at}med.unc.edu

During trans-endothelial migration (TEM), leukocytes use adhesion receptors such as intercellular adhesion molecule-1 (ICAM1) to adhere to the endothelium. In response to this interaction, the endothelium throws up dynamic membrane protrusions, forming a cup that partially surrounds the adherent leukocyte. Little is known about the signaling pathways that regulate cup formation. In this study, we show that RhoG is activated downstream from ICAM1 engagement. This activation requires the intracellular domain of ICAM1. ICAM1 colocalizes with RhoG and binds to the RhoG-specific SH3-containing guanine-nucleotide exchange factor (SGEF). The SH3 domain of SGEF mediates this interaction. Depletion of endothelial RhoG by small interfering RNA does not affect leukocyte adhesion but decreases cup formation and inhibits leukocyte TEM. Silencing SGEF also results in a substantial reduction in RhoG activity, cup formation, and TEM. Together, these results identify a new signaling pathway involving RhoG and its exchange factor SGEF downstream from ICAM1 that is critical for leukocyte TEM.

Abbreviations used in this paper: GEF, guanine-nucleotide exchange factor; HUVEC, human umbilical vein endothelial cell; ICAM1, intercellular adhesion molecule-1; MHC, major histocompatibility complex; miRNA, micro-RNA; PBD, p21-activated kinase–binding domain; ROCK, Rho-associated coil-containing protein kinase; SDF-1, stromal cell–derived factor-1; SGEF, SH3-containing GEF; TEM, trans-endothelial migration; VE, vascular endothelial; wt, wild type.

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

Related Article

RhoG welcomes leukocytes

Mitch Leslie
J. Cell Biol. 2007 178: 1095. [Full Text] [PDF]

This article has been cited by other articles:

• Carman, C. V. (2009). Mechanisms for transcellular diapedesis: probing and pathfinding by `invadosome-like protrusions'. J. Cell Sci. 122: 3025-3035 [Abstract] [Full Text]  
• Muller, W. A. (2009). Mechanisms of Transendothelial Migration of Leukocytes. Circ. Res. 105: 223-230 [Abstract] [Full Text]  
• Elfenbein, A., Rhodes, J. M., Meller, J., Schwartz, M. A., Matsuda, M., Simons, M. (2009). Suppression of RhoG activity is mediated by a syndecan 4-synectin-RhoGDI1 complex and is reversed by PKC{alpha} in a Rac1 activation pathway. JCB 186: 75-83 [Abstract] [Full Text]  
• Huveneers, S., Danen, E. H. J. (2009). Adhesion signaling - crosstalk between integrins, Src and Rho. J. Cell Sci. 122: 1059-1069 [Abstract] [Full Text]  
• Roppenser, B., Roder, A., Hentschke, M., Ruckdeschel, K., Aepfelbacher, M. (2009). Yersinia enterocolitica differentially modulates RhoG activity in host cells. J. Cell Sci. 122: 696-705 [Abstract] [Full Text]  
• Kanters, E., van Rijssel, J., Hensbergen, P. J., Hondius, D., Mul, F. P. J., Deelder, A. M., Sonnenberg, A., van Buul, J. D., Hordijk, P. L. (2008). Filamin B Mediates ICAM-1-driven Leukocyte Transendothelial Migration. J. Biol. Chem. 283: 31830-31839 [Abstract] [Full Text]  
• Barreiro, O., Zamai, M., Yanez-Mo, M., Tejera, E., Lopez-Romero, P., Monk, P. N., Gratton, E., Caiolfa, V. R., Sanchez-Madrid, F. (2008). Endothelial adhesion receptors are recruited to adherent leukocytes by inclusion in preformed tetraspanin nanoplatforms. JCB 183: 527-542 [Abstract] [Full Text]  
• Cowburn, A. S., Condliffe, A. M., Farahi, N., Summers, C., Chilvers, E. R. (2008). Advances in Neutrophil Biology: Clinical Implications. Chest 134: 606-612 [Abstract] [Full Text]  
• Meller, J., Vidali, L., Schwartz, M. A. (2008). Endogenous RhoG is dispensable for integrin-mediated cell spreading but contributes to Rac-independent migration. J. Cell Sci. 121: 1981-1989 [Abstract] [Full Text]  
• Leslie, M. (2007). RhoG welcomes leukocytes. JCB 178: 1095-1095 [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents