Distinct claudins and associated PDZ proteins form different autotypic tight junctions in myelinating Schwann cells

Abstract

The apposed membranes of myelinating Schwann cells are joined by several types of junctional specializations known as autotypic or reflexive junctions. These include tight, gap, and adherens junctions, all of which are found in regions of noncompact myelin: the paranodal loops, incisures of Schmidt-Lanterman, and mesaxons. The molecular components of autotypic tight junctions have not been established. Here we report that two homologues of Discs Lost–multi PDZ domain protein (MUPP)1, and Pals-associated tight junction protein (PATJ), are differentially localized in myelinating Schwann cells and associated with different claudins. PATJ is mainly found at the paranodal loops, where it colocalized with claudin-1. MUPP1 and claudin-5 colocalized in the incisures, and the COOH-terminal region of claudin-5 interacts with MUPP1 in a PSD-95/Disc Large/zona occludens (ZO)-1 (PDZ)-dependent manner. In developing nerves, claudin-5 and MUPP1 appear together in incisures during the first postnatal week, suggesting that they coassemble during myelination. Finally, we show that the incisures also contain four other PDZ proteins that are found in epithelial tight junctions, including three membrane-associated guanylate-kinase proteins (membrane-associated guanylate-kinase inverted-2, ZO-1, and ZO-2) and the adaptor protein Par-3. The presence of these different tight junction proteins in regions of noncompact myelin may be required to maintain the intricate cytoarchitecture of myelinating Schwann cells.

Selective Decrease in Paracellular Conductance of Tight Junctions: Role of the First Extracellular Domain of Claudin-5

“…Our original identification of MBEC1/claudin-5 mRNA and protein expression by the endothelial cells of the BBB (8) has subsequently been confirmed by others (34,41,42). In addition to BBB and other endothelial cells, our studies (8) and those of others (32,35,45,56) have revealed claudin-5 expression in epithelial cells as well as other specialized cell types, including pancreatic acinar cells (45) and myelinating Schwann cells in nerves (44).…”

“…The primer pairs for substitution of Cys 64 with Ser were 5Ј-ACCGGGCACATGCAGTCCAAGGTGTATGAATCT-3Ј and 5Ј-AGATTCATACACCTTGGACTGCATGTGCCCGGT-3Ј. The primer pairs for substitution of the Gln 44 residue with Asn were 5Ј-CAACATCGTGA CGGCGAACACGACTTGGAAGGGGC-3Ј and 5Ј-GCCCCTTCCAAGTCGT GTTCGCCGTCACGATGTTG-3Ј. The primer pairs for replacement of Leu 50 and Trp 51 with Gln and Arg, respectively, were 5Ј-ACGACTTGGAAGGGGC AAAGGATGTCGTGCGTGGT-3Ј and 5Ј-ACCACGCACGACATCCTTTGC CCCTTCCAAGTCGT-3Ј.…”

Modulation of Epithelial Morphology, Monolayer Permeability, and Cell Migration by Growth Arrest Specific 3/Peripheral Myelin Protein 22

“…Typically thought of as a component of compact myelin (Haney et al, 1996), PMP22 has not yet been localized to tight junctions of PNS myelin. Based on the effects of PMP22 on epithelial paracellular permeability, the protein could have a similar role in PNS myelin at claudin-1-and -5-positive autotypic tight junctions (Poliak et al, 2002). Therefore, modulating PMP22 in an epithelial model may provide some clues as to the function of the protein in PNS myelin.…”

Analysis of congenital hypomyelinating Egr2 Lo/Lo nerves identifies Sox2 as an inhibitor of Schwann cell differentiation and myelination

“…Additionally, myelin sheath structural proteins, such as Claudin 5 and Mupp1 (16), which interact with each other in the Schmidt-Lanterman incisures, were present in the DEC ALL data set. These results encouraged us to perform quantitative RT-PCR analysis to examine the expression of other DEC ALL genes, including EphB6, p21, Pea15, Nr4a2, and the potassium ion channel KcnK1 in immature cultured Schwann cells, and in developing and injured nerves.…”