Original Article

Determination of Cell Adhesion Sites of Neuropilin-1

Correspondence to: Hajime Fujisawa, Group of Developmental Neurobiology, Division of Biological Science, Nagoya University Graduate School of Science, Chikusa-ku, Nagoya 464-8602, Japan. Tel:+81-52-789-2978 Fax:+81-52-789-2979 E-mail:fujisawa{at}bio.nagoya-u.ac.jp.

Neuropilin-1 is a type 1 membrane protein with three distinct functions. First, it can mediate cell adhesion via a heterophilic molecular interaction. Second, in neuronal cells, neuropilin-1 binds the class 3 semaphorins, which are neuronal chemorepellents, and plays a role in the directional guidance of axons. Neuropilin-1 is expected to form complexes with the plexinA subfamily members and mediate the semaphorin-elicited inhibitory signals into neurons. Third, in endothelial cells, neuropilin-1 binds a potent endothelial cell mitogen, vascular endothelial growth factor (VEGF)₁₆₅, and regulates vessel formation. Though the binding sites in neuropilin-1 for the class 3 semaphorins and VEGF₁₆₅ have been analyzed, the sites involved in cell adhesion activity of the molecule have not been identified. In this study, we produced a variety of mutant neuropilin-1s and tested their cell adhesion activity. We showed that the b1 and b2 domains within the extracellular segment of neuropilin-1 were required for the cell adhesion activity, and peptides with an 18–amino acid stretch in the b1 and b2 domains were sufficient to induce the cell adhesion activity. In addition, we demonstrated that the cell adhesion ligands for neuropilin-1 were proteins and distributed in embryonic mesenchymal cells but distinct from the class 3 semaphorins, VEGF, or plexins.

Key Words: neuropilin-1, cell adhesion, cell aggregation, semaphorins, mutant protein

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

This article has been cited by other articles:

• Glinka, Y., Prud'homme, G. J. (2008). Neuropilin-1 is a receptor for transforming growth factor {beta}-1, activates its latent form, and promotes regulatory T cell activity. J. Leukoc. Biol. 84: 302-310 [Abstract] [Full Text]  
• Narazaki, M., Segarra, M., Tosato, G. (2008). Neuropilin-2: A New Molecular Target for Antiangiogenic and Antitumor Strategies. JNCI J Natl Cancer Inst 100: 81-83 [Full Text]  
• Jaalouk, D. E., Ozawa, M. G., Sun, J., Lahdenranta, J., Schlingemann, R. O., Pasqualini, R., Arap, W. (2007). The Original Pathologische Anatomie Leiden-Endothelium Monoclonal Antibody Recognizes a Vascular Endothelial Growth Factor Binding Site within Neuropilin-1. Cancer Res. 67: 9623-9629 [Abstract] [Full Text]  
• Wolman, M. A., Regnery, A. M., Becker, T., Becker, C. G., Halloran, M. C. (2007). Semaphorin3D Regulates Axon Axon Interactions by Modulating Levels of L1 Cell Adhesion Molecule. J. Neurosci. 27: 9653-9663 [Abstract] [Full Text]  
• Vander Kooi, C. W., Jusino, M. A., Perman, B., Neau, D. B., Bellamy, H. D., Leahy, D. J. (2007). Structural basis for ligand and heparin binding to neuropilin B domains. Proc. Natl. Acad. Sci. USA 104: 6152-6157 [Abstract] [Full Text]  
• Nguyen, Q.-D., Rodrigues, S., Rodrigue, C. M., Rivat, C., Grijelmo, C., Bruyneel, E., Emami, S., Attoub, S., Gespach, C. (2006). Inhibition of vascular endothelial growth factor (VEGF)-165 and semaphorin 3A-mediated cellular invasion and tumor growth by the VEGF signaling inhibitor ZD4190 in human colon cancer cells and xenografts.. Molecular Cancer Therapeutics 5: 2070-2077 [Abstract] [Full Text]  
• Williams, C. K., Li, J.-L., Murga, M., Harris, A. L., Tosato, G. (2006). Up-regulation of the Notch ligand Delta-like 4 inhibits VEGF-induced endothelial cell function. Blood 107: 931-939 [Abstract] [Full Text]  
• Murga, M., Fernandez-Capetillo, O., Tosato, G. (2005). Neuropilin-1 regulates attachment in human endothelial cells independently of vascular endothelial growth factor receptor-2. Blood 105: 1992-1999 [Abstract] [Full Text]  
• Wolman, M. A., Liu, Y., Tawarayama, H., Shoji, W., Halloran, M. C. (2004). Repulsion and Attraction of Axons by Semaphorin3D Are Mediated by Different Neuropilins In Vivo. J. Neurosci. 24: 8428-8435 [Abstract] [Full Text]  
• Abdulhussein, R., McFadden, C., Fuentes-Prior, P., Vogel, W. F. (2004). Exploring the Collagen-binding Site of the DDR1 Tyrosine Kinase Receptor. J. Biol. Chem. 279: 31462-31470 [Abstract] [Full Text]  
• Sahay, A., Molliver, M. E., Ginty, D. D., Kolodkin, A. L. (2003). Semaphorin 3F Is Critical for Development of Limbic System Circuitry and Is Required in Neurons for Selective CNS Axon Guidance Events. J. Neurosci. 23: 6671-6680 [Abstract] [Full Text]  
• Yamada, Y., Oike, Y., Ogawa, H., Ito, Y., Fujisawa, H., Suda, T., Takakura, N. (2003). Neuropilin-1 on hematopoietic cells as a source of vascular development. Blood 101: 1801-1809 [Abstract] [Full Text]  
• Mamluk, R., Gechtman, Z.'e., Kutcher, M. E., Gasiunas, N., Gallagher, J., Klagsbrun, M. (2002). Neuropilin-1 Binds Vascular Endothelial Growth Factor 165, Placenta Growth Factor-2, and Heparin via Its b1b2 Domain. J. Biol. Chem. 277: 24818-24825 [Abstract] [Full Text]  
• Gu, C., Limberg, B. J., Whitaker, G. B., Perman, B., Leahy, D. J., Rosenbaum, J. S., Ginty, D. D., Kolodkin, A. L. (2002). Characterization of Neuropilin-1 Structural Features That Confer Binding to Semaphorin 3A and Vascular Endothelial Growth Factor 165. J. Biol. Chem. 277: 18069-18076 [Abstract] [Full Text]  
• Kawasaki, T., Bekku, Y., Suto, F., Kitsukawa, T., Taniguchi, M., Nagatsu, I., Nagatsu, T., Itoh, K., Yagi, T., Fujisawa, H. (2002). Requirement of neuropilin 1-mediated Sema3A signals in patterning of the sympathetic nervous system. Development 129: 671-680 [Abstract] [Full Text]  
• Yamada, Y., Takakura, N., Yasue, H., Ogawa, H., Fujisawa, H., Suda, T. (2001). Exogenous clustered neuropilin 1 enhances vasculogenesis and angiogenesis. Blood 97: 1671-1678 [Abstract] [Full Text]  
• Kobuke, K., Furukawa, Y., Sugai, M., Tanigaki, K., Ohashi, N., Matsumori, A., Sasayama, S., Honjo, T., Tashiro, K. (2001). ESDN, a Novel Neuropilin-like Membrane Protein Cloned from Vascular Cells with the Longest Secretory Signal Sequence among Eukaryotes, Is Up-regulated after Vascular Injury. J. Biol. Chem. 276: 34105-34114 [Abstract] [Full Text]  

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