Modulation of epithelial morphology, monolayer permeability, and cell migration by growth arrest specific 3/peripheral myelin protein 22

Peripheral myelin protein 22 (PMP22) is associated with a subset of hereditary peripheral neuropathies. Although predominantly recognized as a transmembrane constituent of peripheral nerve myelin, PMP22 is localized to epithelial and endothelial cell-cell junctions, where its function remains unknown. In this report, we investigated the role of PMP22 in epithelial biology. Expression of human PMP22 (hPMP22) slows cell growth and induces a flattened morphology in Madin-Darby canine kidney (MDCK) cells. The transepithelial electrical resistance (TER) and paracellular flux of MDCK monolayers are elevated by hPMP22 expression. After calcium switch, peptides corresponding to the second, but not the first, extracellular loop of PMP22 perturb the recovery of TER and paracellular flux. Finally, subsequent to wounding, epithelial monolayers expressing hPMP22 fail to migrate normally. These results indicate that PMP22 is capable of modulating several aspects of epithelial cell biology, including junctional permeability and wound closure.