Protein kinase C (PKC) is important for tight junction assembly. Immunofluorescent localization of the tight junction protein zonula occludens 1 (ZO-1) during the Madin-Darby canine kidney (MDCK) cell calcium switch. In low-calcium media MDCK cells are round and have little cell-cell contact. Under these conditions, ZO-1 is found in the cell interior and has little, if any, membrane staining, A. After 2 hours incubation in normal calcium media, MDCK cells undergo significant changes in cell shape and make extensive cell-cell contact along the lateral portions of the plasma membrane. B, Here, ZO-1 has redistributed to areas of cell-cell contact with little apparent intracellular staining. This process is blocked by treatment with either 500 nM calphostin C, C, or 25 |M H7, D, inhibitors of PKC. These results suggest that PKC plays a role in regulating tight junction assembly. Similar studies have demonstrated roles for a number of other signaling molecules, including calcium and G proteins, in the assembly of tight junctions [12, 13, 16-19, 37, 44-46]. An analogous set of signaling events is likely responsible for tight junction reassembly after ischemia. (From Stuart and Nigam ; with permission.)
Signalling molecules that may be involved in tight junction assembly. Model of the potential signaling events involved in tight junction assembly. Tight junction assembly probably depends on a complex interplay of several signaling molecules, including protein kinase C (PKC), calcium (Ca2+), heterotrimeric G proteins, small guanodine triphosphatases (Rab/Rho), and tyrosine kinases [13-16, 18, 37, 44-53]. Although it is not clear how this process is initiated, it depends on cell-cell contact and involves wide-scale changes in levels of intracellular free calcium. Receptor/CAM—cell adhesion molecule; DAG—diacylglyc-erol; ER—endoplasmic reticulum; Ga—alpha subunit of GTP-binding protein; IP3—inositol trisphosphate. (From Denker and Nigam ; with permission.)
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