Junctional adhesion molecule-A is critical for the formation of pseudocanaliculi and modulates E-cadherin expression in hepatic cells

Genevieve Konopka, Jackie Tekiela, Moriah Iverson, Clive Wells, Stephen A. Duncan

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)28137-28148
Number of pages12
JournalJournal of Biological Chemistry
Volume282
Issue number38
DOIs
StatePublished - Sep 21 2007

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Junctional Adhesion Molecule A
Cadherins
Tight Junction Proteins
Hepatocytes
Adherens Junctions
Tight Junctions
Cells
Gene expression
Intercellular Junctions
Cell Nucleus
Adhesion
Hepatocellular Carcinoma
Epithelial Cells
Gene Expression
Cell Line
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Junctional adhesion molecule-A is critical for the formation of pseudocanaliculi and modulates E-cadherin expression in hepatic cells. / Konopka, Genevieve; Tekiela, Jackie; Iverson, Moriah; Wells, Clive; Duncan, Stephen A.

In: Journal of Biological Chemistry, Vol. 282, No. 38, 21.09.2007, p. 28137-28148.

Research output: Contribution to journalArticle

Konopka, Genevieve ; Tekiela, Jackie ; Iverson, Moriah ; Wells, Clive ; Duncan, Stephen A. / Junctional adhesion molecule-A is critical for the formation of pseudocanaliculi and modulates E-cadherin expression in hepatic cells. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 38. pp. 28137-28148.
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