J. Cell Biol., Volume 142, Number 1, July 13, 1998 139-151

Direct Interaction of CASK/LIN-2 and Syndecan Heparan Sulfate Proteoglycan and Their Overlapping Distribution in Neuronal Synapses

Yi-Ping Hsueh,^* Fu-Chia Yang,^* Viktor Kharazia, Scott Naisbitt,^* Alexandra R. Cohen,^§ Richard J. Weinberg, and Morgan Sheng^*

^* Howard Hughes Medical Institute and Department of Neurobiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114;  Department of Cell Biology and Anatomy, University of North Carolina, Chapel Hill, North Carolina 27599; ^§ Department of Cell Biology and Internal Medicine, Yale School of Medicine, New Haven, Connecticut 06520

CASK, the rat homolog of a gene (LIN-2) required for vulval differentiation in Caenorhabditis elegans, is expressed in mammalian brain, but its function in neurons is unknown. CASK is distributed in a punctate somatodendritic pattern in neurons. By immunogold EM, CASK protein is concentrated in synapses, but is also present at nonsynaptic membranes and in intracellular compartments. This immunolocalization is consistent with biochemical studies showing the presence of CASK in soluble and synaptosomal membrane fractions and its enrichment in postsynaptic density fractions of rat brain. By yeast two-hybrid screening, a specific interaction was identified between the PDZ domain of CASK and the COOH terminal tail of syndecan-2, a cell surface heparan sulfate proteoglycan (HSPG). The interaction was confirmed by coimmunoprecipitation from heterologous cells. In brain, syndecan-2 localizes specifically at synaptic junctions where it shows overlapping distribution with CASK, consistent with an interaction between these proteins in synapses. Cell surface HSPGs can bind to extracellular matrix proteins, and are required for the action of various heparin-binding polypeptide growth/differentiation factors. The synaptic localization of CASK and syndecan suggests a potential role for these proteins in adhesion and signaling at neuronal synapses.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Waites, C. L., Specht, C. G., Hartel, K., Leal-Ortiz, S., Genoux, D., Li, D., Drisdel, R. C., Jeyifous, O., Cheyne, J. E., Green, W. N., Montgomery, J. M., Garner, C. C. (2009). Synaptic SAP97 Isoforms Regulate AMPA Receptor Dynamics and Access to Presynaptic Glutamate. J. Neurosci. 29: 4332-4345 [Abstract] [Full Text]  
• Hayashida, K., Stahl, P. D., Park, P. W. (2008). Syndecan-1 Ectodomain Shedding Is Regulated by the Small GTPase Rab5. J. Biol. Chem. 283: 35435-35444 [Abstract] [Full Text]  
• Whiteford, J. R., Ko, S., Lee, W., Couchman, J. R. (2008). Structural and Cell Adhesion Properties of Zebrafish Syndecan-4 Are Shared with Higher Vertebrates. J. Biol. Chem. 283: 29322-29330 [Abstract] [Full Text]  
• Chao, H.-W., Hong, C.-J., Huang, T.-N., Lin, Y.-L., Hsueh, Y.-P. (2008). SUMOylation of the MAGUK protein CASK regulates dendritic spinogenesis. JCB 182: 141-155 [Abstract] [Full Text]  
• Ojeh, N., Pekovic, V., Jahoda, C., Maatta, A. (2008). The MAGUK-family protein CASK is targeted to nuclei of the basal epidermis and controls keratinocyte proliferation. J. Cell Sci. 121: 2705-2717 [Abstract] [Full Text]  
• Lin, Y.-L., Lei, Y.-T., Hong, C.-J., Hsueh, Y.-P. (2007). Syndecan-2 induces filopodia and dendritic spine formation via the neurofibromin-PKA-Ena/VASP pathway. JCB 177: 829-841 [Abstract] [Full Text]  
• Atasoy, D., Schoch, S., Ho, A., Nadasy, K. A., Liu, X., Zhang, W., Mukherjee, K., Nosyreva, E. D., Fernandez-Chacon, R., Missler, M., Kavalali, E. T., Sudhof, T. C. (2007). Deletion of CASK in mice is lethal and impairs synaptic function. Proc. Natl. Acad. Sci. USA 104: 2525-2530 [Abstract] [Full Text]  
• McQuade, K. J., Beauvais, D. M., Burbach, B. J., Rapraeger, A. C. (2006). Syndecan-1 regulates {alpha}v{beta}5 integrin activity in B82L fibroblasts. J. Cell Sci. 119: 2445-2456 [Abstract] [Full Text]  
• Rhiner, C., Gysi, S., Frohli, E., Hengartner, M. O., Hajnal, A. (2005). Syndecan regulates cell migration and axon guidance in C. elegans. Development 132: 4621-4633 [Abstract] [Full Text]  
• Zordan, M. A., Massironi, M., Ducato, M. G., te Kronnie, G., Costa, R., Reggiani, C., Chagneau, C., Martin, J.-R., Megighian, A. (2005). Drosophila CAKI/CMG Protein, a Homolog of Human CASK, Is Essential for Regulation of Neurotransmitter Vesicle Release. J. Neurophysiol. 94: 1074-1083 [Abstract] [Full Text]  
• Tkachenko, E., Rhodes, J. M., Simons, M. (2005). Syndecans: New Kids on the Signaling Block. Circ. Res. 96: 488-500 [Abstract] [Full Text]  
• Glodowski, D. R., Wright, T., Martinowich, K., Chang, H. C.-H., Beach, D., Rongo, C. (2005). Distinct LIN-10 Domains Are Required for Its Neuronal Function, Its Epithelial Function, and Its Synaptic Localization. Mol. Biol. Cell 16: 1417-1426 [Abstract] [Full Text]  
• Zhai, R. G., Bellen, H. J. (2004). The Architecture of the Active Zone in the Presynaptic Nerve Terminal. Physiology 19: 262-270 [Abstract] [Full Text]  
• Zhang, X., Cheng, M., Chintala, S. K. (2004). Kainic Acid-Mediated Upregulation of Matrix Metalloproteinase-9 Promotes Retinal Degeneration. IOVS 45: 2374-2383 [Abstract] [Full Text]  
• Peng, J., Kim, M. J., Cheng, D., Duong, D. M., Gygi, S. P., Sheng, M. (2004). Semiquantitative Proteomic Analysis of Rat Forebrain Postsynaptic Density Fractions by Mass Spectrometry. J. Biol. Chem. 279: 21003-21011 [Abstract] [Full Text]  
• Leonoudakis, D., Conti, L. R., Radeke, C. M., McGuire, L. M. M., Vandenberg, C. A. (2004). A Multiprotein Trafficking Complex Composed of SAP97, CASK, Veli, and Mint1 Is Associated with Inward Rectifier Kir2 Potassium Channels. J. Biol. Chem. 279: 19051-19063 [Abstract] [Full Text]  
• Kusano, Y., Yoshitomi, Y., Munesue, S., Okayama, M., Oguri, K. (2004). Cooperation of Syndecan-2 and Syndecan-4 among Cell Surface Heparan Sulfate Proteoglycans in the Actin Cytoskeletal Organization of Lewis Lung Carcinoma Cells. J Biochem 135: 129-137 [Abstract] [Full Text]  
• Wilsie, L. C., Orlando, R. A. (2003). The Low Density Lipoprotein Receptor-related Protein Complexes with Cell Surface Heparan Sulfate Proteoglycans to Regulate Proteoglycan-mediated Lipoprotein Catabolism. J. Biol. Chem. 278: 15758-15764 [Abstract] [Full Text]  
• Lim, S.-T., Longley, R. L., Couchman, J. R., Woods, A. (2003). Direct Binding of Syndecan-4 Cytoplasmic Domain to the Catalytic Domain of Protein Kinase Calpha (PKCalpha ) Increases Focal Adhesion Localization of PKCalpha. J. Biol. Chem. 278: 13795-13802 [Abstract] [Full Text]  
• Schuh, K., Uldrijan, S., Gambaryan, S., Roethlein, N., Neyses, L. (2003). Interaction of the Plasma Membrane Ca2+ Pump 4b/CI with the Ca2+/Calmodulin-dependent Membrane-associated Kinase CASK. J. Biol. Chem. 278: 9778-9783 [Abstract] [Full Text]  
• Biederer, T., Sara, Y., Mozhayeva, M., Atasoy, D., Liu, X., Kavalali, E. T., Sudhof, T. C. (2002). SynCAM, a Synaptic Adhesion Molecule That Drives Synapse Assembly. Science 297: 1525-1531 [Abstract] [Full Text]  
• Maximov, A., Bezprozvanny, I. (2002). Synaptic Targeting of N-Type Calcium Channels in Hippocampal Neurons. J. Neurosci. 22: 6939-6952 [Abstract] [Full Text]  
• Lim, I. A., Hall, D. D., Hell, J. W. (2002). Selectivity and Promiscuity of the First and Second PDZ Domains of PSD-95 and Synapse-associated Protein 102. J. Biol. Chem. 277: 21697-21711 [Abstract] [Full Text]  
• Tabuchi, K., Biederer, T., Butz, S., Sudhof, T. C. (2002). CASK Participates in Alternative Tripartite Complexes in which Mint 1 Competes for Binding with Caskin 1, a Novel CASK-Binding Protein. J. Neurosci. 22: 4264-4273 [Abstract] [Full Text]  
• Horowitz, A., Tkachenko, E., Simons, M. (2002). Fibroblast growth factor-specific modulation of cellular response by syndecan-4. JCB 157: 715-725 [Abstract] [Full Text]  
• Denhez, F., Wilcox-Adelman, S. A., Baciu, P. C., Saoncella, S., Lee, S., French, B., Neveu, W., Goetinck, P. F. (2002). Syndesmos, a Syndecan-4 Cytoplasmic Domain Interactor, Binds to the Focal Adhesion Adaptor Proteins Paxillin and Hic-5. J. Biol. Chem. 277: 12270-12274 [Abstract] [Full Text]  
• Hung, A. Y., Sheng, M. (2002). PDZ Domains: Structural Modules for Protein Complex Assembly. J. Biol. Chem. 277: 5699-5702 [Full Text]  
• Szklarczyk, A., Lapinska, J., Rylski, M., McKay, R. D. G., Kaczmarek, L. (2002). Matrix Metalloproteinase-9 Undergoes Expression and Activation during Dendritic Remodeling in Adult Hippocampus. J. Neurosci. 22: 920-930 [Abstract] [Full Text]  
• Fallon, L., Moreau, F., Croft, B. G., Labib, N., Gu, W.-J., Fon, E. A. (2002). Parkin and CASK/LIN-2 Associate via a PDZ-mediated Interaction and Are Co-localized in Lipid Rafts and Postsynaptic Densities in Brain. J. Biol. Chem. 277: 486-491 [Abstract] [Full Text]  
• Passini, M. A., Wolfe, J. H. (2001). Widespread Gene Delivery and Structure-Specific Patterns of Expression in the Brain after Intraventricular Injections of Neonatal Mice with an Adeno-Associated Virus Vector. J. Virol. 75: 12382-12392 [Abstract] [Full Text]  
• Biederer, T., Sudhof, T. C. (2001). CASK and Protein 4.1 Support F-actin Nucleation on Neurexins. J. Biol. Chem. 276: 47869-47876 [Abstract] [Full Text]  
• Vaccaro, P., Brannetti, B., Montecchi-Palazzi, L., Philipp, S., Citterich, M. H., Cesareni, G., Dente, L. (2001). Distinct Binding Specificity of the Multiple PDZ Domains of INADL, a Human Protein with Homology to INAD from Drosophila melanogaster. J. Biol. Chem. 276: 42122-42130 [Abstract] [Full Text]  
• Zhang, W., Benson, D. L. (2001). Stages of Synapse Development Defined by Dependence on F-Actin. J. Neurosci. 21: 5169-5181 [Abstract] [Full Text]  
• Bennett, V., Baines, A. J. (2001). Spectrin and Ankyrin-Based Pathways: Metazoan Inventions for Integrating Cells Into Tissues. Physiol. Rev. 81: 1353-1392 [Abstract] [Full Text]  
• Hsueh, Y.-P., Roberts, A. M., Volta, M., Sheng, M., Roberts, R. G. (2001). Bipartite Interaction between Neurofibromatosis Type I Protein (Neurofibromin) and Syndecan Transmembrane Heparan Sulfate Proteoglycans. J. Neurosci. 21: 3764-3770 [Abstract] [Full Text]  
• Zimmermann, P., Tomatis, D., Rosas, M., Grootjans, J., Leenaerts, I., Degeest, G., Reekmans, G., Coomans, C., David, G. (2001). Characterization of Syntenin, a Syndecan-binding PDZ Protein, as a Component of Cell Adhesion Sites and Microfilaments. Mol. Biol. Cell 12: 339-350 [Abstract] [Full Text]  
• Bandtlow, C. E., Zimmermann, D. R. (2000). Proteoglycans in the Developing Brain: New Conceptual Insights for Old Proteins. Physiol. Rev. 80: 1267-1290 [Abstract] [Full Text]  
• Ethell, I. M., Hagihara, K., Miura, Y., Irie, F., Yamaguchi, Y. (2000). Synbindin, A Novel Syndecan-2-binding Protein in Neuronal Dendritic Spines. JCB 151: 53-68 [Abstract] [Full Text]  
• Modrowski, D., Basle, M., Lomri, A., Marie, P. J. (2000). Syndecan-2 Is Involved in the Mitogenic Activity and Signaling of Granulocyte-Macrophage Colony-stimulating Factor in Osteoblasts. J. Biol. Chem. 275: 9178-9185 [Abstract] [Full Text]  
• Baciu, P., Saoncella, S, Lee, S., Denhez, F, Leuthardt, D, Goetinck, P. (2000). Syndesmos, a protein that interacts with the cytoplasmic domain of syndecan-4, mediates cell spreading and actin cytoskeletal organization. J. Cell Sci. 113: 315-324 [Abstract]  
• Garner, M. H., Kong, Y. (1999). Lens Epithelium and Fiber Na,K-ATPases: Distribution and Localization by Immunocytochemistry. IOVS 40: 2291-2298 [Abstract] [Full Text]  
• Hsueh, Y.-P., Sheng, M. (1999). Regulated Expression and Subcellular Localization of Syndecan Heparan Sulfate Proteoglycans and the Syndecan-Binding Protein CASK/LIN-2 during Rat Brain Development. J. Neurosci. 19: 7415-7425 [Abstract] [Full Text]  
• Volk, R., Schwartz, J. J., Li, J., Rosenberg, R. D., Simons, M. (1999). The Role of Syndecan Cytoplasmic Domain in Basic Fibroblast Growth Factor-dependent Signal Transduction. J. Biol. Chem. 274: 24417-24424 [Abstract] [Full Text]  
• Butz, S., Fernandez-Chacon, R., Schmitz, F., Jahn, R., Sudhof, T. C. (1999). The Subcellular Localizations of Atypical Synaptotagmins III and VI. SYNAPTOTAGMIN III IS ENRICHED IN SYNAPSES AND SYNAPTIC PLASMA MEMBRANES BUT NOT IN SYNAPTIC VESICLES. J. Biol. Chem. 274: 18290-18296 [Abstract] [Full Text]  
• ZIMMERMANN, P., DAVID, G. (1999). The syndecans, tuners of transmembrane signaling. FASEB J. 13: 91-100 [Abstract] [Full Text]  
• Saoncella, S., Echtermeyer, F., Denhez, F., Nowlen, J. K., Mosher, D. F., Robinson, S. D., Hynes, R. O., Goetinck, P. F. (1999). Syndecan-4 signals cooperatively with integrins in a Rhodependent manner in the assembly of focal adhesions and actin stress fibers. Proc. Natl. Acad. Sci. USA 96: 2805-2810 [Abstract] [Full Text]  
• Lauri, S. E., Kaukinen, S., Kinnunen, T., Ylinen, A., Imai, S., Kaila, K., Taira, T., Rauvala, H. (1999). Reg1ulatory Role and Molecular Interactions of a Cell-Surface Heparan Sulfate Proteoglycan (N-syndecan) in Hippocampal Long-Term Potentiation. J. Neurosci. 19: 1226-1235 [Abstract] [Full Text]  
• Borg, J.-P., Lopez-Figueroa, M. O., de Taddeo-Borg, M., Kroon, D. E., Turner, R. S., Watson, S. J., Margolis, B. (1999). Molecular Analysis of the X11-mLin-2/CASK Complex in Brain. J. Neurosci. 19: 1307-1316 [Abstract] [Full Text]  
• Ethell, I. M., Yamaguchi, Y. (1999). Cell Surface Heparan Sulfate Proteoglycan Syndecan-2 Induces the Maturation of Dendritic Spines in Rat Hippocampal Neurons. JCB 144: 575-586 [Abstract] [Full Text]  
• Echtermeyer, F, Baciu, P., Saoncella, S, Ge, Y, Goetinck, P. (1999). Syndecan-4 core protein is sufficient for the assembly of focal adhesions and actin stress fibers. J. Cell Sci. 112: 3433-3441 [Abstract]  
• Jiang, P., Lagenaur, C. F., Narayanan, V. (1999). Integrin-associated Protein Is a Ligand for the P84 Neural Adhesion Molecule. J. Biol. Chem. 274: 559-562 [Abstract] [Full Text]  
• Missler, M., Hammer, R. E., Sudhof, T. C. (1998). Neurexophilin Binding to alpha -Neurexins. A SINGLE LNS DOMAIN FUNCTIONS AS AN INDEPENDENTLY FOLDING LIGAND-BINDING UNIT. J. Biol. Chem. 273: 34716-34723 [Abstract] [Full Text]  
• Ott, V. L., Rapraeger, A. C. (1998). Tyrosine Phosphorylation of Syndecan-1 and -4 Cytoplasmic Domains in Adherent B82 Fibroblasts. J. Biol. Chem. 273: 35291-35298 [Abstract] [Full Text]  
• Borg, J.-P., Straight, S. W., Kaech, S. M., de Taddeo-Borg, M., Kroon, D. E., Karnak, D., Turner, R. S., Kim, S. K., Margolis, B. (1998). Identification of an Evolutionarily Conserved Heterotrimeric Protein Complex Involved in Protein Targeting. J. Biol. Chem. 273: 31633-31636 [Abstract] [Full Text]  
• Sugita, S., Saito, F., Tang, J., Satz, J., Campbell, K., Sudhof, T. C. (2001). A stoichiometric complex of neurexins and dystroglycan in brain. JCB 154: 435-446 [Abstract] [Full Text]  
• Biederer, T., Sudhof, T. C. (2000). Mints as Adaptors. DIRECT BINDING TO NEUREXINS AND RECRUITMENT OF Munc18. J. Biol. Chem. 275: 39803-39806 [Abstract] [Full Text]  
• Grootjans, J. J., Reekmans, G., Ceulemans, H., David, G. (2000). Syntenin-Syndecan Binding Requires Syndecan-Synteny and the Co-operation of Both PDZ Domains of Syntenin. J. Biol. Chem. 275: 19933-19941 [Abstract] [Full Text]  
• Martinez-Estrada, O. M., Villa, A., Breviario, F., Orsenigo, F., Dejana, E., Bazzoni, G. (2001). Association of Junctional Adhesion Molecule with Calcium/calmodulin-dependent Serine Protein Kinase (CASK/LIN-2) in Human Epithelial Caco-2 Cells. J. Biol. Chem. 276: 9291-9296 [Abstract] [Full Text]  
• Misawa, H., Kawasaki, Y., Mellor, J., Sweeney, N., Jo, K., Nicoll, R. A., Bredt, D. S. (2001). Contrasting Localizations of MALS/LIN-7 PDZ Proteins in Brain and Molecular Compensation in Knockout Mice. J. Biol. Chem. 276: 9264-9272 [Abstract] [Full Text]  
• Jaulin-Bastard, F., Saito, H., Le Bivic, A., Ollendorff, V., Marchetto, S., Birnbaum, D., Borg, J.-P. (2001). The ERBB2/HER2 Receptor Differentially Interacts with ERBIN and PICK1 PSD-95/DLG/ZO-1 Domain Proteins. J. Biol. Chem. 276: 15256-15263 [Abstract] [Full Text]  
• Woods, A., Couchman, J. R. (2000). Integrin Modulation by Lateral Association. J. Biol. Chem. 275: 24233-24236 [Full Text]  
• Park, P. W., Reizes, O., Bernfield, M. (2000). Cell Surface Heparan Sulfate Proteoglycans: Selective Regulators of Ligand-Receptor Encounters. J. Biol. Chem. 275: 29923-29926 [Full Text]  
• Davidson, B. L., Stein, C. S., Heth, J. A., Martins, I., Kotin, R. M., Derksen, T. A., Zabner, J., Ghodsi, A., Chiorini, J. A. (2000). From the Cover: Recombinant adeno-associated virus type 2, 4, and 5 vectors: Transduction of variant cell types and regions in the mammalian central nervous system. Proc. Natl. Acad. Sci. USA 97: 3428-3432 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents