Scientific Article
previous document  unige:11233  next document
add to browser collection

The junctional adhesion molecule (JAM) family members JAM-2 and JAM-3 associate with the cell polarity protein PAR-3: a possible role for JAMs in endothelial cell polarity

Ebnet, Klaus
Kuhn, Annegret
Kiefer, Friedemann
Butz, Stefan
Zander, Kerstin
Meyer zu Brickwedde, M. K.
show hidden authors show all authors [1 - 10]
Published in Journal of Cell Science. 2003, vol. 116, no. Pt 19, p. 3879-3891
Abstract Tight junctions play a central role in the establishment of cell polarity in vertebrate endothelial and epithelial cells. A ternary protein complex consisting of the cell polarity proteins PAR-3 and PAR-6 and the atypical protein kinase C localizes at tight junctions and is crucial for tight junction formation. We have recently shown that PAR-3 directly associates with the junctional adhesion molecule (JAM), which suggests that the ternary complex is targeted to tight junctions of epithelial cells through PAR-3 binding to JAM. The expression of JAM-related proteins by endothelial cells prompted us to test whether recruitment of the ternary complex in endothelial cells can occur through binding to JAM-2, JAM-3, endothelial cell-selective adhesion molecule (ESAM) or coxsackie- and adenovirus receptor (CAR). Here we show that the two JAM-related proteins JAM-2 and JAM-3 directly associate with PAR-3. The association between PAR-3 and JAM-2/-3 is mediated through the first PDZ domain of PAR-3. In agreement with the predominant expression of JAM-2 and JAM-3 in endothelial cells, we found that PAR-3 is expressed by endothelial cells in vivo and is localized at cell contacts of cultured endothelial cells. PAR-3 associates with JAM-2/-3 but not with the JAM-related Ig-superfamily members ESAM or CAR. In addition, we show that the tight junction-associated protein ZO-1 associates with JAM-2/-3 in a PDZ domain-dependent manner. Using ectopic expression of JAM-2 in CHO cells, we show that the junctional localization of JAM-2 is regulated by serine phosphorylation and that its clustering at cell-cell contacts recruits endogenous PAR-3 and ZO-1. Our findings suggest that JAM-2 affects endothelial cell junctions by its regulated clustering at intercellular contacts, and they support a role for JAM-2, and possibly JAM-3, in tight junction formation of endothelial cells.
Keywords AnimalsCHO CellsCOS CellsCarrier Proteins/ metabolismCell Adhesion Molecules/ metabolismCell Polarity/ physiologyCells, CulturedCercopithecus aethiopsCloning, MolecularCricetinaeCricetulusEndothelial Cells/ metabolismEpithelial Cells/metabolismHumansImmunoglobulins/ metabolismImmunohistochemistryMembrane Proteins/ metabolismMicePhosphorylationProtein BindingProtein Structure, TertiarySerine/metabolismTight Junctions/metabolism
Stable URL
Full text
PMID: 12953056
105 hits and 278 downloads since 2010-08-27
Export document
Format :
Citation style :