期刊
JOURNAL OF CELL BIOLOGY
卷 160, 期 5, 页码 729-740出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200211047
关键词
epithelia; Dbl; intercellular adhesion; actin; microtubules
类别
资金
- Biotechnology and Biological Sciences Research Council [G18784] Funding Source: Medline
- Medical Research Council [G0100558] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
- MRC [G0100558] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [G18784] Funding Source: researchfish
- Medical Research Council [G0100558] Funding Source: researchfish
Rho family GTRases 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据