The role of Junctional Adhesion Molecule-A (JAM-A) in cell polarity and mitosis

Basic data for this project

Description

Vertebrate epithelial and endothelial cells are embedded in cellular sheets that line the inner surfaces of the body. The individual cells have distinct membrane domains, an apical domain which is free and a basolateral domain which is in contact with other cells and the extracellular matrix; this is commonly referred to as apico-basal membrane polarity. The apical and basolateral membrane domains are separated by tight junctions (TJ) at the apical region of the cell-cell contact sites. Recent evidence indicates that signaling from and to TJs regulates cell proliferation, differentiation and apoptosis. Our interest is focused on a small family of cell adhesion molecules localized at TJs, the Junctional Adhesion Molecules (JAMs). We have previously identified several PDZ domain proteins associated with JAMs including the cell polarity protein PAR-3, and we have found indirect evidence that homophilic JAM-A interactions induce signalling events required for TJ and apico-basal membrane polarity formation. In preliminary experiments, we have found that JAM-A is phosphorylated by PKC in vitro and in vivo. The specific aims of the present proposal is: (1) to analyze the signaling pathway induced by JAM-A homophilic interactions, (2) to analyze the role of JAM-A phosphorylation for TJ and cell polarity formation, (3) to analyze the role of JAM-A and JAM-A phosphorylation during mitosis.