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

This Article Full Text Full Text (PDF, 688K) PPT slides of all figures 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 Benais-Pont, G. Articles by Matter, K. Search for Related Content PubMed PubMed Citation Articles by Benais-Pont, G. Articles by Matter, K. Social Bookmarking                      What's this?

¹ Department of Cell Biology, University of Geneva, 1211 Geneva, Switzerland
² Division of Cell Biology, Institute of Ophthalmology, University College London, EC1V 9EL London, UK
³ Department of Physiology, Center for Research and Advanced Studies, Mexico, D.F., 07360 Mexico
⁴ Division of Cell Sciences, School of Biological Sciences, University of Southampton, SO16 7PX Southampton, UK
⁵ Curie Institute, Research Section, Paris 7505, France

Address correspondence to Karl Matter, Div. of Cell Biology, Institute of Ophthalmology, University College London, Bath St., London EC1V 9EL, UK. Tel.: 44-20-7608-4014. Fax: 44-20-7608-4034. E-mail: k.matter{at}ucl.ac.uk; or Maria S. Balda, Div. of Cell Biology, Institute of Ophthalmology, University College London, Bath St., London EC1V 9EL, UK. Tel.: 44-20-7608-4014. Fax: 44-20-7608-4034. E-mail: m.balda{at}ucl.ac.uk

Rho family GTPases are important regulators of epithelial tight junctions (TJs); however, little is known about how the GTPases themselves are controlled during TJ assembly and function. We have identified and cloned a canine guanine nucleotide exchange factor (GEF) of the Dbl family of proto-oncogenes that activates Rho and associates with TJs. Based on sequence similarity searches and immunological and functional data, this protein is the canine homologue of human GEF-H1 and mouse Lfc, two previously identified Rho-specific exchange factors known to associate with microtubules in nonpolarized cells. In agreement with these observations, immunofluorescence of proliferating MDCK cells revealed that the endogenous canine GEF-H1/Lfc associates with mitotic spindles. Functional analysis based on overexpression and RNA interference in polarized MDCK cells revealed that this exchange factor for Rho regulates paracellular permeability of small hydrophilic tracers. Although overexpression resulted in increased size-selective paracellular permeability, such cell lines exhibited a normal overall morphology and formed fully assembled TJs as determined by measuring transepithelial resistance and by immunofluorescence and freeze-fracture analysis. These data indicate that GEF-H1/Lfc is a component of TJs and functions in the regulation of epithelial permeability.

Key Words: epithelia; Dbl; intercellular adhesion; actin; microtubules

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

This article has been cited by other articles:

• Van Itallie, C. M., Holmes, J., Bridges, A., Gookin, J. L., Coccaro, M. R., Proctor, W., Colegio, O. R., Anderson, J. M. (2008). The density of small tight junction pores varies among cell types and is increased by expression of claudin-2. J. Cell Sci. 121: 298-305 [Abstract] [Full Text]  
• Samarin, S. N., Ivanov, A. I., Flatau, G., Parkos, C. A., Nusrat, A. (2007). Rho/Rho-associated Kinase-II Signaling Mediates Disassembly of Epithelial Apical Junctions. Mol. Biol. Cell 18: 3429-3439 [Abstract] [Full Text]  
• Siegrist, S. E., Doe, C. Q. (2007). Microtubule-induced cortical cell polarity. Genes Dev. 21: 483-496 [Abstract] [Full Text]  
• Fan, L., Sebe, A., Peterfi, Z., Masszi, A., Thirone, A. C.P., Rotstein, O. D., Nakano, H., McCulloch, C. A., Szaszi, K., Mucsi, I., Kapus, A. (2007). Cell Contact-dependent Regulation of Epithelial-Myofibroblast Transition via the Rho-Rho Kinase-Phospho-Myosin Pathway. Mol. Biol. Cell 18: 1083-1097 [Abstract] [Full Text]  
• Kavanagh, E., Buchert, M., Tsapara, A., Choquet, A., Balda, M. S., Hollande, F., Matter, K. (2006). Functional interaction between the ZO-1-interacting transcription factor ZONAB/DbpA and the RNA processing factor symplekin. J. Cell Sci. 119: 5098-5105 [Abstract] [Full Text]  
• Adachi, M., Inoko, A., Hata, M., Furuse, K., Umeda, K., Itoh, M., Tsukita, S. (2006). Normal Establishment of Epithelial Tight Junctions in Mice and Cultured Cells Lacking Expression of ZO-3, a Tight-Junction MAGUK Protein. Mol. Cell. Biol. 26: 9003-9015 [Abstract] [Full Text]  
• Otani, T., Ichii, T., Aono, S., Takeichi, M. (2006). Cdc42 GEF Tuba regulates the junctional configuration of simple epithelial cells. JCB 175: 135-146 [Abstract] [Full Text]  
• Shen, L., Black, E. D., Witkowski, E. D., Lencer, W. I., Guerriero, V., Schneeberger, E. E., Turner, J. R. (2006). Myosin light chain phosphorylation regulates barrier function by remodeling tight junction structure. J. Cell Sci. 119: 2095-2106 [Abstract] [Full Text]  
• Sourisseau, T., Georgiadis, A., Tsapara, A., Ali, R. R., Pestell, R., Matter, K., Balda, M. S. (2006). Regulation of PCNA and Cyclin D1 Expression and Epithelial Morphogenesis by the ZO-1-Regulated Transcription Factor ZONAB/DbpA.. Mol. Cell. Biol. 26: 2387-2398 [Abstract] [Full Text]  
• Birukova, A. A., Adyshev, D., Gorshkov, B., Bokoch, G. M., Birukov, K. G., Verin, A. D. (2006). GEF-H1 is involved in agonist-induced human pulmonary endothelial barrier dysfunction. Am. J. Physiol. Lung Cell. Mol. Physiol. 290: L540-L548 [Abstract] [Full Text]  
• Tsapara, A., Matter, K., Balda, M. S. (2006). The Heat-Shock Protein Apg-2 Binds to the Tight Junction Protein ZO-1 and Regulates Transcriptional Activity of ZONAB. Mol. Biol. Cell 17: 1322-1330 [Abstract] [Full Text]  
• Ogawa, K., Wada, H., Okada, N., Harada, I., Nakajima, T., Pasquale, E. B., Tsuyama, S. (2006). EphB2 and ephrin-B1 expressed in the adult kidney regulate the cytoarchitecture of medullary tubule cells through Rho family GTPases. J. Cell Sci. 119: 559-570 [Abstract] [Full Text]  
• Matsuzawa, T., Kuwae, A., Abe, A. (2005). Enteropathogenic Escherichia coli Type III Effectors EspG and EspG2 Alter Epithelial Paracellular Permeability. Infect. Immun. 73: 6283-6289 [Abstract] [Full Text]  
• Szaszi, K., Sirokmany, G., Ciano-Oliveira, C. D., Rotstein, O. D., Kapus, A. (2005). Depolarization induces Rho-Rho kinase-mediated myosin light chain phosphorylation in kidney tubular cells. Am. J. Physiol. Cell Physiol. 289: C673-C685 [Abstract] [Full Text]  
• Bakal, C. J., Finan, D., LaRose, J., Wells, C. D., Gish, G., Kulkarni, S., DeSepulveda, P., Wilde, A., Rottapel, R. (2005). The Rho GTP exchange factor Lfc promotes spindle assembly in early mitosis. Proc. Natl. Acad. Sci. USA 102: 9529-9534 [Abstract] [Full Text]  
• Gon, Y., Wood, M. R., Kiosses, W. B., Jo, E., Sanna, M. G., Chun, J., Rosen, H. (2005). S1P3 receptor-induced reorganization of epithelial tight junctions compromises lung barrier integrity and is potentiated by TNF. Proc. Natl. Acad. Sci. USA 102: 9270-9275 [Abstract] [Full Text]  
• Matlin, K. S. (2005). Clues to occludin. Focus on "Knockdown of occludin expression leads to diverse phenotypic alterations in epithelial cells". Am. J. Physiol. Cell Physiol. 288: C1191-C1192 [Full Text]  
• Yu, A. S. L., McCarthy, K. M., Francis, S. A., McCormack, J. M., Lai, J., Rogers, R. A., Lynch, R. D., Schneeberger, E. E. (2005). Knockdown of occludin expression leads to diverse phenotypic alterations in epithelial cells. Am. J. Physiol. Cell Physiol. 288: C1231-C1241 [Abstract] [Full Text]  
• Hoenderop, J. G. J., Nilius, B., Bindels, R. J. M. (2005). Calcium Absorption Across Epithelia. Physiol. Rev. 85: 373-422 [Abstract] [Full Text]  
• Ohnishi, H., Nakahara, T., Furuse, K., Sasaki, H., Tsukita, S., Furuse, M. (2004). JACOP, a Novel Plaque Protein Localizing at the Apical Junctional Complex with Sequence Similarity to Cingulin. J. Biol. Chem. 279: 46014-46022 [Abstract] [Full Text]  
• Umeda, K., Matsui, T., Nakayama, M., Furuse, K., Sasaki, H., Furuse, M., Tsukita, S. (2004). Establishment and Characterization of Cultured Epithelial Cells Lacking Expression of ZO-1. J. Biol. Chem. 279: 44785-44794 [Abstract] [Full Text]  
• Guillemot, L., Hammar, E., Kaister, C., Ritz, J., Caille, D., Jond, L., Bauer, C., Meda, P., Citi, S. (2004). Disruption of the cingulin gene does not prevent tight junction formation but alters gene expression. J. Cell Sci. 117: 5245-5256 [Abstract] [Full Text]  
• Bazzoni, G., Dejana, E. (2004). Endothelial Cell-to-Cell Junctions: Molecular Organization and Role in Vascular Homeostasis. Physiol. Rev. 84: 869-901 [Abstract] [Full Text]  
• Kohler, K., Louvard, D., Zahraoui, A. (2004). Rab13 regulates PKA signaling during tight junction assembly. JCB 165: 175-180 [Abstract] [Full Text]  
• Hayashi, H., Szaszi, K., Coady-Osberg, N., Furuya, W., Bretscher, A. P., Orlowski, J., Grinstein, S. (2004). Inhibition and Redistribution of NHE3, the Apical Na+/H+ Exchanger, by Clostridium difficile Toxin B. JGP 123: 491-504 [Abstract] [Full Text]  
• Shiu, Y.-T., Li, S., Marganski, W. A., Usami, S., Schwartz, M. A., Wang, Y.-L., Dembo, M., Chien, S. (2004). Rho Mediates the Shear-Enhancement of Endothelial Cell Migration and Traction Force Generation. Biophys. J 86: 2558-2565 [Abstract] [Full Text]  
• Stamatovic, S. M., Keep, R. F., Kunkel, S. L., Andjelkovic, A. V. (2003). Potential role of MCP-1 in endothelial cell tight junction `opening': signaling via Rho and Rho kinase. J. Cell Sci. 116: 4615-4628 [Abstract] [Full Text]  
• SOMLYO, A. P., SOMLYO, A. V. (2003). Ca2+ Sensitivity of Smooth Muscle and Nonmuscle Myosin II: Modulated by G Proteins, Kinases, and Myosin Phosphatase. Physiol. Rev. 83: 1325-1358 [Abstract] [Full Text]  
• Matter, K., Balda, M. S. (2003). Holey barrier: claudins and the regulation of brain endothelial permeability. JCB 161: 459-460 [Abstract] [Full Text]  

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