title: Nectin-like molecule-1/TSLL1/SynCAM3: a neural tissue-specific immunoglobulin-like cell-cell adhesion molecule localizing at non-junctional contact sites of presynaptic nerve terminals, axons and glia cell processes.
abstract: Nectins are Ca2+-independent immunoglobulin-like cell-cell adhesion molecules and comprise a family of four members. At the mossy fiber terminals of hippocampus, nectin-1 and nectin-3 localize at the presynaptic and postsynaptic sides of synaptic junctions, respectively, and their trans-interactions play a role in formation of synapses in cooperation with N-cadherin. Nectins are associated with the actin cytoskeleton through afadin, a nectin- and actin-filament-binding protein. Five nectin-like molecules (Necls) which have domain structures similar to those of nectins have been identified and here we characterize Necl-1/TSLL1/SynCAM3, from now on referred to as Necl-1. Tissue distribution analysis showed that Necl-1 was specifically expressed in the neural tissue. Immunofluorescence and immunoelectron microscopy revealed that Necl-1 localized at the contact sites among axons, their terminals, and glia cell processes that cooperatively formed synapses, axon bundles and myelinated axons. Necl-1 showed Ca2+-independent homophilic cell-cell adhesion activity. It furthermore showed Ca2+-independent heterophilic cell-cell adhesion activity with Necl-2/IGSF4/RA175/SgIGSF/TSLC1/SynCAM1 from now on referred to as Necl-2, nectin-1 and nectin-3, but not with Necl-5 or nectin-2. The C-terminal cytoplasmic region of Necl-1 did not bind afadin but bound membrane-associated guanylate kinase subfamily members that contain the L27 domain, including Dlg3, Pals2 and CASK. These results indicate that Necl-1 is a neural-tissue-specific Ca2+-independent immunoglobulin-like cell-cell adhesion molecule which potentially has membrane-associated guanylate kinase subfamily member-binding activity and localizes at the non-junctional cell-cell contact sites.
authors.affiliation: Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Osaka, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kakunaga
authors.forename: Wataru
authors.initials: W
authors.lastname: Ikeda
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Itoh
authors.forename: Maki
authors.initials: M
authors.lastname: Deguchi-Tawarada
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Ohtsuka
authors.forename: Akira
authors.initials: A
authors.lastname: Mizoguchi
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism; D001369:Axons / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002448:Cell Adhesion; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication; D002460:Cell Line; D002531:Cerebellum / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D015723:Gene Library; D051528:Guanylate Kinases; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism* / Q000502:physiology; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D009186:Myelin Sheath / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012583:Schwann Cells / Q000378:metabolism; D016622:Silver Staining; D013997:Time Factors; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D020798:Two-Hybrid System Techniques
chemical_list: D000199:Actins; D000951:Antigens, Neoplasm; C403514:CADM1 protein, human; D015820:Cadherins; C498598:Cadm1 protein, mouse; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; C116869:DLG3 protein, human; D007136:Immunoglobulins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C476587:Taa1 protein, mouse; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C106868:CASK kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases; D002118:Calcium