title: Peripheral myelin protein 22 is a constituent of intercellular junctions in epithelia.
abstract: Alterations in peripheral myelin protein 22 (PMP22) gene expression are associated with a host of heritable demyelinating peripheral neuropathies, yet the function of the protein remains unknown. PMP22 expression is highest in myelinating Schwann cells of peripheral nerves; however, significant levels of PMP22 mRNAs can be detected in a variety of non-neural tissue, including epithelia. To date, PMP22 protein expression and localization in non-neural tissues have not been studied in detail. In adult rat liver and intestine, 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 anti-occludin and anti-PMP22 antibodies. Nonionic detergent extraction of cultured epithelial cells did not solubilize PMP22, as the majority of the protein remained in the detergent insoluble fraction, as did ZO-1 and occludin. We also observed the targeting of exogenous myc-tagged 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 intercellular junctions of epithelia and may indicate a similar function in myelinating Schwann cells. Furthermore, our findings could provide an explanation for certain phenotypes of PMP22 neuropathy mice that cannot be accounted for by dysmyelination.
authors.affiliation: Department of Neuroscience, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL 32610, USA. notterp@ufbi.ufl.edu
authors.forename: L
authors.initials: L
authors.lastname: Notterpek
authors.forename: K J
authors.initials: KJ
authors.lastname: Roux
authors.forename: S A
authors.initials: SA
authors.lastname: Amici
authors.forename: A
authors.initials: A
authors.lastname: Yazdanpour
authors.forename: C
authors.initials: C
authors.lastname: Rahner
authors.forename: B S
authors.initials: BS
authors.lastname: Fletcher
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism; D015870:Gene Expression; D007150:Immunohistochemistry; D007365:Intercellular Junctions / Q000378:metabolism*; D007739:L Cells; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D062793:Occludin; D010523:Peripheral Nervous System Diseases / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D062826:Zonula Occludens-1 Protein
chemical_list: D008565:Membrane Proteins; D009185:Myelin Proteins; D062793:Occludin; C568986:Ocln protein, mouse; C568987:Ocln protein, rat; D010750:Phosphoproteins; C489545:Pmp22 protein, mouse; C489546:Pmp22 protein, rat; D012333:RNA, Messenger; C569043:Tjp1 protein, mouse; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein