Identification of a tight junction-associated guanine nucleotide exchange factor that activates Rho and regulates paracellular permeability


Benais-Pont, Gaelle, Punn, Anu, Flores-Maldonado, Catalina, Eckert, Judith, Raposo, Graca, Fleming, Tom P., Cereijido, Marcelino, Balda, Maria S. and Matter, Karl (2003) Identification of a tight junction-associated guanine nucleotide exchange factor that activates Rho and regulates paracellular permeability. Journal of Cell Biology, 160, (5), 729-740. (doi:10.1083/jcb.200211047).

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Original Publication URL: http://dx.doi.org/10.1083/jcb.200211047

Description/Abstract

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.

Item Type: Article
ISSNs: 0021-9525 (print)
Related URLs:
Keywords: epithelia, dbl, intercellular adhesion, actin, microtubules
Subjects: Q Science > QP Physiology
Q Science > QH Natural history > QH301 Biology
Divisions: University Structure - Pre August 2011 > School of Medicine > Developmental Origins of Health and Disease
ePrint ID: 25247
Date Deposited: 07 Apr 2006
Last Modified: 27 Mar 2014 18:14
URI: http://eprints.soton.ac.uk/id/eprint/25247

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