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

This Article Full Text Full Text (PDF, 409K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Niethammer, P. Articles by Schachner, M. Search for Related Content PubMed PubMed Citation Articles by Niethammer, P. Articles by Schachner, M. Social Bookmarking                      What's this?

¹ Zentrum für Molekulare Neurobiologie, Universität Hamburg, D-20246 Hamburg, Germany
² Department of Biochemistry, Institute of Medical Science, University of Tokyo, Minato-ku, 108-8639 Tokyo, Japan

Address correspondence to Melitta Schachner, Zentrum für Molekulare Neurobiologie, Universität Hamburg, Martinistrasse 52, D-20246 Hamburg, Germany. Tel.: 49-40-42803-6246. Fax: 49-40-42803-6248. E-mail: melitta.schachner{at}zmnh.uni-hamburg.de

The neural cell adhesion molecule (NCAM) has been reported to stimulate neuritogenesis either via nonreceptor tyrosine kinases or fibroblast growth factor (FGF) receptor. Here we show that lipid raft association of NCAM is crucial for activation of the nonreceptor tyrosine kinase pathway and induction of neurite outgrowth. Transfection of hippocampal neurons of NCAM-deficient mice revealed that of the three major NCAM isoforms only NCAM140 can act as a homophilic receptor that induces neurite outgrowth. Disruption of NCAM140 raft association either by mutation of NCAM140 palmitoylation sites or by lipid raft destruction attenuates activation of the tyrosine focal adhesion kinase and extracellular signal–regulated kinase 1/2, completely blocking neurite outgrowth. Likewise, NCAM-triggered neurite outgrowth is also completely blocked by a specific FGF receptor inhibitor, indicating that cosignaling via raft-associated kinases and FGF receptor is essential for neuritogenesis.

Key Words: neurite outgrowth; NCAM; lipid rafts; palmitoylation; FGF receptor

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

This article has been cited by other articles:

• Brackenbury, W. J., Djamgoz, M. B.A., Isom, L. L. (2008). An Emerging Role for Voltage-Gated Na+ Channels in Cellular Migration: Regulation of Central Nervous System Development and Potentiation of Invasive Cancers. Neuroscientist 14: 571-583 [Abstract]  
• Bodrikov, V., Sytnyk, V., Leshchyns'ka, I., den Hertog, J., Schachner, M. (2008). NCAM induces CaMKII{alpha}-mediated RPTP{alpha} phosphorylation to enhance its catalytic activity and neurite outgrowth. JCB 182: 1185-1200 [Abstract] [Full Text]  
• Ponimaskin, E., Dityateva, G., Ruonala, M. O., Fukata, M., Fukata, Y., Kobe, F., Wouters, F. S., Delling, M., Bredt, D. S., Schachner, M., Dityatev, A. (2008). Fibroblast Growth Factor-Regulated Palmitoylation of the Neural Cell Adhesion Molecule Determines Neuronal Morphogenesis. J. Neurosci. 28: 8897-8907 [Abstract] [Full Text]  
• Brackenbury, W. J., Davis, T. H., Chen, C., Slat, E. A., Detrow, M. J., Dickendesher, T. L., Ranscht, B., Isom, L. L. (2008). Voltage-Gated Na+ Channel {beta}1 Subunit-Mediated Neurite Outgrowth Requires Fyn Kinase and Contributes to Postnatal CNS Development In Vivo. J. Neurosci. 28: 3246-3256 [Abstract] [Full Text]  
• Roduit, C., van der Goot, F. G., De Los Rios, P., Yersin, A., Steiner, P., Dietler, G., Catsicas, S., Lafont, F., Kasas, S. (2008). Elastic Membrane Heterogeneity of Living Cells Revealed by Stiff Nanoscale Membrane Domains. Biophys. J 94: 1521-1532 [Abstract] [Full Text]  
• Diestel, S., Schaefer, D., Cremer, H., Schmitz, B. (2007). NCAM is ubiquitylated, endocytosed and recycled in neurons. J. Cell Sci. 120: 4035-4049 [Abstract] [Full Text]  
• Conchonaud, F., Nicolas, S., Amoureux, M.-C., Menager, C., Marguet, D., Lenne, P.-F., Rougon, G., Matarazzo, V. (2007). Polysialylation Increases Lateral Diffusion of Neural Cell Adhesion Molecule in the Cell Membrane. J. Biol. Chem. 282: 26266-26274 [Abstract] [Full Text]  
• Buff, H., Smith, A. C., Korey, C. A. (2007). Genetic Modifiers of Drosophila Palmitoyl-Protein Thioesterase 1-Induced Degeneration. Genetics 176: 209-220 [Abstract] [Full Text]  
• Wang, X., Hisha, H., Cui, W., Song, C., Mizokami, T., Okazaki, S., Li, Q., Feng, W., Kato, J., Jiang, S., Fan, H., Ikehara, S. (2007). The characteristics of hematopoietic stem cells from autoimmune-prone mice and the role of neural cell adhesion molecules in abnormal proliferation of these cells in MRL/lpr mice. haematol 92: 300-307 [Abstract] [Full Text]  
• Brown, D. A. (2006). Lipid Rafts, Detergent-Resistant Membranes, and Raft Targeting Signals.. Physiology 21: 430-439 [Abstract] [Full Text]  
• Sanchez-Heras, E., Howell, F. V., Williams, G., Doherty, P. (2006). The Fibroblast Growth Factor Receptor Acid Box Is Essential for Interactions with N-Cadherin and All of the Major Isoforms of Neural Cell Adhesion Molecule. J. Biol. Chem. 281: 35208-35216 [Abstract] [Full Text]  
• Senkov, O., Sun, M., Weinhold, B., Gerardy-Schahn, R., Schachner, M., Dityatev, A. (2006). Polysialylated Neural Cell Adhesion Molecule Is Involved in Induction of Long-Term Potentiation and Memory Acquisition and Consolidation in a Fear-Conditioning Paradigm.. J. Neurosci. 26: 10888-109898 [Abstract] [Full Text]  
• Wang, X., Hisha, H., Taketani, S., Inaba, M., Li, Q., Cui, W., Song, C., Fan, T., Cui, Y., Guo, K., Yang, G., Fan, H., Lian, Z., Gershwin, M. E., Ikehara, S. (2005). Neural Cell Adhesion Molecule Contributes to Hemopoiesis-Supporting Capacity of Stromal Cell Lines. Stem Cells 23: 1389-1399 [Abstract] [Full Text]  
• Shogomori, H., Hammond, A. T., Ostermeyer-Fay, A. G., Barr, D. J., Feigenson, G. W., London, E., Brown, D. A. (2005). Palmitoylation and Intracellular Domain Interactions Both Contribute to Raft Targeting of Linker for Activation of T Cells. J. Biol. Chem. 280: 18931-18942 [Abstract] [Full Text]  
• Causeret, M., Taulet, N., Comunale, F., Favard, C., Gauthier-Rouviere, C. (2005). N-Cadherin Association with Lipid Rafts Regulates Its Dynamic Assembly at Cell-Cell Junctions in C2C12 Myoblasts. Mol. Biol. Cell 16: 2168-2180 [Abstract] [Full Text]  
• Santuccione, A., Sytnyk, V., Leshchyns'ka, I., Schachner, M. (2005). Prion protein recruits its neuronal receptor NCAM to lipid rafts to activate p59fyn and to enhance neurite outgrowth. JCB 169: 341-354 [Abstract] [Full Text]  
• Herincs, Z., Corset, V., Cahuzac, N., Furne, C., Castellani, V., Hueber, A.-O., Mehlen, P. (2005). DCC association with lipid rafts is required for netrin-1-mediated axon guidance. J. Cell Sci. 118: 1687-1692 [Abstract] [Full Text]  
• Bodrikov, V., Leshchyns'ka, I., Sytnyk, V., Overvoorde, J., den Hertog, J., Schachner, M. (2005). RPTP{alpha} is essential for NCAM-mediated p59fyn activation and neurite elongation. JCB 168: 127-139 [Abstract] [Full Text]  
• Davis, T. H., Chen, C., Isom, L. L. (2004). Sodium Channel {beta}1 Subunits Promote Neurite Outgrowth in Cerebellar Granule Neurons. J. Biol. Chem. 279: 51424-51432 [Abstract] [Full Text]  
• Crnic, I., Strittmatter, K., Cavallaro, U., Kopfstein, L., Jussila, L., Alitalo, K., Christofori, G. (2004). Loss of Neural Cell Adhesion Molecule Induces Tumor Metastasis by Up-regulating Lymphangiogenesis. Cancer Res. 64: 8630-8638 [Abstract] [Full Text]  
• Washbourne, P., Dityatev, A., Scheiffele, P., Biederer, T., Weiner, J. A., Christopherson, K. S., El-Husseini, A. (2004). Cell Adhesion Molecules in Synapse Formation. J. Neurosci. 24: 9244-9249 [Abstract] [Full Text]  
• Dityatev, A., Dityateva, G., Sytnyk, V., Delling, M., Toni, N., Nikonenko, I., Muller, D., Schachner, M. (2004). Polysialylated Neural Cell Adhesion Molecule Promotes Remodeling and Formation of Hippocampal Synapses. J. Neurosci. 24: 9372-9382 [Abstract] [Full Text]  
• Falk, J., Thoumine, O., Dequidt, C., Choquet, D., Faivre-Sarrailh, C. (2004). NrCAM Coupling to the Cytoskeleton Depends on Multiple Protein Domains and Partitioning into Lipid Rafts. Mol. Biol. Cell 15: 4695-4709 [Abstract] [Full Text]  
• Butchbach, M. E. R., Tian, G., Guo, H., Lin, C.-l. G. (2004). Association of Excitatory Amino Acid Transporters, Especially EAAT2, with Cholesterol-rich Lipid Raft Microdomains: IMPORTANCE FOR EXCITATORY AMINO ACID TRANSPORTER LOCALIZATION AND FUNCTION. J. Biol. Chem. 279: 34388-34396 [Abstract] [Full Text]  
• Cambon, K., Hansen, S. M., Venero, C., Herrero, A. I., Skibo, G., Berezin, V., Bock, E., Sandi, C. (2004). A Synthetic Neural Cell Adhesion Molecule Mimetic Peptide Promotes Synaptogenesis, Enhances Presynaptic Function, and Facilitates Memory Consolidation. J. Neurosci. 24: 4197-4204 [Abstract] [Full Text]  
• Decker, L., ffrench-Constant, C. (2004). Lipid Rafts and Integrin Activation Regulate Oligodendrocyte Survival. J. Neurosci. 24: 3816-3825 [Abstract] [Full Text]  
• Islam, R., Kristiansen, L. V., Romani, S., Garcia-Alonso, L., Hortsch, M. (2004). Activation of EGF Receptor Kinase by L1-mediated Homophilic Cell Interactions. Mol. Biol. Cell 15: 2003-2012 [Abstract] [Full Text]  
• Thorp, E. B., Gallagher, T. M. (2004). Requirements for CEACAMs and Cholesterol during Murine Coronavirus Cell Entry. J. Virol. 78: 2682-2692 [Abstract] [Full Text]  
• Shin, D. M., Korada, S., Raballo, R., Shashikant, C. S., Simeone, A., Taylor, J. R., Vaccarino, F. (2004). Loss of Glutamatergic Pyramidal Neurons in Frontal and Temporal Cortex Resulting from Attenuation of FGFR1 Signaling Is Associated with Spontaneous Hyperactivity in Mice. J. Neurosci. 24: 2247-2258 [Abstract] [Full Text]  
• Bukalo, O., Fentrop, N., Lee, A. Y. W., Salmen, B., Law, J. W. S., Wotjak, C. T., Schweizer, M., Dityatev, A., Schachner, M. (2004). Conditional Ablation of the Neural Cell Adhesion Molecule Reduces Precision of Spatial Learning, Long-Term Potentiation, and Depression in the CA1 Subfield of Mouse Hippocampus. J. Neurosci. 24: 1565-1577 [Abstract] [Full Text]  
• Papoucheva, E., Dumuis, A., Sebben, M., Richter, D. W., Ponimaskin, E. G. (2004). The 5-Hydroxytryptamine(1A) Receptor Is Stably Palmitoylated, and Acylation Is Critical for Communication of Receptor with Gi Protein. J. Biol. Chem. 279: 3280-3291 [Abstract] [Full Text]  
• Seidenfaden, R., Krauter, A., Schertzinger, F., Gerardy-Schahn, R., Hildebrandt, H. (2003). Polysialic Acid Directs Tumor Cell Growth by Controlling Heterophilic Neural Cell Adhesion Molecule Interactions. Mol. Cell. Biol. 23: 5908-5918 [Abstract] [Full Text]  
• Peng, H., Derrick, B. E., Martinez, J. L. Jr (2003). Identification of Upregulated SCG10 mRNA Expression Associated with Late-Phase Long-Term Potentiation in the Rat Hippocampal Schaffer-CA1 Pathway In Vivo. J. Neurosci. 23: 6617-6626 [Abstract] [Full Text]  
• Leshchyns'ka, I., Sytnyk, V., Morrow, J. S., Schachner, M. (2003). Neural cell adhesion molecule (NCAM) association with PKC{beta}2 via {beta}I spectrin is implicated in NCAM-mediated neurite outgrowth. JCB 161: 625-639 [Abstract] [Full Text]  
• Stockklausner, C., Klocker, N. (2003). Surface Expression of Inward Rectifier Potassium Channels Is Controlled by Selective Golgi Export. J. Biol. Chem. 278: 17000-17005 [Abstract] [Full Text]  
• Nakai, Y., Kamiguchi, H. (2002). Migration of nerve growth cones requires detergent-resistant membranes in a spatially defined and substrate-dependent manner. JCB 159: 1097-1108 [Abstract] [Full Text]  
• Delling, M., Wischmeyer, E., Dityatev, A., Sytnyk, V., Veh, R. W., Karschin, A., Schachner, M. (2002). The Neural Cell Adhesion Molecule Regulates Cell-Surface Delivery of G-Protein-Activated Inwardly Rectifying Potassium Channels Via Lipid Rafts. J. Neurosci. 22: 7154-7164 [Abstract] [Full Text]  

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