title: 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.
authors.affiliation: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Poliak
authors.forename: Sean
authors.initials: S
authors.lastname: Matlis
authors.forename: Christoph
authors.initials: C
authors.lastname: Ullmer
authors.forename: Steven S
authors.initials: SS
authors.lastname: Scherer
authors.forename: Elior
authors.initials: E
authors.lastname: Peles
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D002352:Carrier Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D062445:Claudin-1; D062507:Claudin-5; D004847:Epithelial Cells / Q000737:chemistry / Q000648:ultrastructure; D005136:Eye Proteins; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D009409:Nerve Crush; D009413:Nerve Fibers, Myelinated / Q000737:chemistry; D009431:Neural Conduction / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D011901:Ranvier's Nodes / Q000737:chemistry; D051381:Rats; D012583:Schwann Cells / Q000737:chemistry* / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000737:chemistry / Q000166:cytology*; D062725:Tight Junction Proteins; D019108:Tight Junctions / Q000737:chemistry*
chemical_list: D000906:Antibodies; C568108:CLDN1 protein, human; D002352:Carrier Proteins; D062445:Claudin-1; D062507:Claudin-5; C568114:Cldn1 protein, rat; C491510:Cldn5 protein, rat; D005136:Eye Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C491749:Mpdz protein, rat; C107903:PATJ protein, human; D012333:RNA, Messenger; D062725:Tight Junction Proteins