Junctional adhesion molecule-A is critical for the formation of pseudocanaliculi and modulates E-cadherin expression in hepatic cells. J Biol Chem 2007 Sep 21;282(38):28137-48
Date
07/12/2007Pubmed ID
17623668DOI
10.1074/jbc.M703592200Scopus ID
2-s2.0-34948890139 (requires institutional sign-in at Scopus site) 44 CitationsAbstract
Hepatocytes are polarized epithelial cells whose function depends upon their ability to distinguish between the apical and basolateral surfaces that are located at intercellular tight junctions. It has been proposed that the signaling cascades originating at these junctions influence cellular activity by controlling gene expression in the cell nucleus. To assess the validity of this proposal with regard to hepatocytes, we depleted expression of the tight junction protein junctional adhesion molecule-A (JAM-A) in the HepG2 human hepatocellular carcinoma cell line. Reduction of JAM-A resulted in a striking change in cell morphology, with cells forming sheets 1-2 cells thick instead of the normal multilayered clusters. In the absence of JAM-A, other tight junction proteins were mislocalized, and pseudocanaliculi, which form the apical face of the hepatocyte, were consequently absent. There was a strong transcriptional induction of the adherens junction protein E-cadherin in cells with reduced levels of JAM-A. This increase in E-cadherin was partially responsible for the observed alterations in cell morphology and mislocalization of tight junction proteins. We therefore propose the existence of a novel mechanism of cross-talk between specific components of tight and adherens junctions that can be utilized to regulate adhesion between hepatic cells.
Author List
Konopka G, Tekiela J, Iverson M, Wells C, Duncan SAMESH terms used to index this publication - Major topics in bold
Adherens JunctionsAnimals
Bile Canaliculi
Cadherins
Cell Adhesion Molecules
Cell Line, Tumor
Cell Nucleus
Gene Expression Regulation
Hepatocytes
Humans
Immunoglobulins
Liver
Liver Neoplasms
Mice
Mice, Inbred C57BL
Models, Biological
Receptors, Cell Surface
Tight Junctions
