Peripheral myelin protein 22 is a constituent of intercellular junctions in epithelia

Alterations in peripheral myelin protein 22 (PMP22) gene expression are ass ociated with a host of heritable demyelinating peripheral neuropathies, yet the function of the protein remains unknown. PMP22 expression is highest i n myelinating Schwann cells of peripheral nerves; however, significant leve ls of PMP22 mRNAs can be detected in a variety of non-neural tissue, includ ing epithelia. To date, PMP22 protein expression and localization in non-ne ural tissues have not been studied in detail. In adult rat liver and intest ine, and cultured epithelial cells, we detected PMP22-like immunoreactivity associated with markers of the tight junctional complex, including zonula occludens 1 (ZO-1) and occludin. Upon disruption of intercellular contacts, PMP22 was internalized into vesicles that were immunoreactive for both ant i-occludin and anti-PMP22 antibodies. Nonionic detergent extraction of cult ured epithelial cells did not solubilize PMP22, as the majority of the prot ein remained in the detergent insoluble fraction, as did ZO-1 and occludin. We also observed the targeting of exogenous myctagged PMP22 to apical cell junctions in polarized epithelia and to anti-ZO-1 antibody immunoreactive cell contacts of L fibroblasts. These studies support a role for PMP22 at i ntercellular junctions of epithelia and may indicate a similar function in myelinating Schwann cells, Furthermore, our findings could provide an expla nation for certain phenotypes of PMP22 neuropathy mice that cannot be accou nted for by dysmyelination.