From The Discovery of Neuropilin to the Determination of Its Adhesion Sites

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 515)


Neuropilin (NRP) and plexin (Plex) that are now known to be semaphorin receptors were initially identified as antigens for monoclonal antibodies (MAbs) that bound to particular neuropiles and plexiform layers of theXenopustadpole optic tectum, several years before the discovery of semaphorin. The extracellular segment of the NRP protein is a mosaic of 3 functionally different protein motifs that are thought to be involved in molecular and/or cellular interactions, suggesting that NRP serves in a various cell-cell interaction by binding a variety of molecules. The first identified function of NRP was the cell adhesion activity; Cell reaggregation study using NRP-expressing cell lines revealed that NRP can mediate cell adhesion via heterophilic molecular interaction. Later, NRP was shown to bind semaphorins and vascular endothelial growth factor (VEGF). It was also shown that NRP makes receptor complexes with Plex to propagate semaphorin signals.


Vascular Endothelial Growth Factor Retinal Ganglion Cell Plexiform Layer Optic Tectum Discoidin Domain Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Luo Y, Raible D, Raper JA. Collapsin: A protein in brain that induces the collapse and paralysis of neuronal growth cones. Cell 1993; 75:217–227.PubMedCrossRefGoogle Scholar
  2. 2.
    He Z, Tessier-Lavigne M. Neuropilin is a receptor for the axonal chemorepellent semaphorin III. Cell 1997; 90:739–751.PubMedCrossRefGoogle Scholar
  3. 3.
    Kolodkin AL, Levengood DV, Rowe EG et al. Neuropilin is a semaphorin III receptor. Cell 1997; 90:753–762.PubMedCrossRefGoogle Scholar
  4. 4.
    Comeau MR, Johnson R, DuBose RF et al. A poxvirus-encoded semaphorin induces cytokine production from monocytes and binds to a novel cellular semaphorin receptor, VESPR. Immunity 1998; 8:473–482.PubMedCrossRefGoogle Scholar
  5. 5.
    Winberg ML, Noordermeer JN, Tamagnone L et al. Plexin A is a neuronal scmaphorin receptor that controls axon guidance. Cell 1998; 95:903–916.PubMedCrossRefGoogle Scholar
  6. 6.
    Takagi S, Tsuji T, Amagai T et al. Specific cell surface labels in the visual centers ofXenopus laevistadpole identified using monoclonal antibodies. Dev Biol 1987; 122:90–100.PubMedCrossRefGoogle Scholar
  7. 7.
    Sperry RW. Chemoaffinity in the orderly growth of nerve fibre patterns and connection. Proc Nail Acad Sci USA 1963; 50:703–710.CrossRefGoogle Scholar
  8. 8.
    Fujisawa H, Takagi S, Hirata T. Growth-associated expression of a membrane protein, neuropilin, inXenopusoptic nerve fibers. Dev Neurosci 1995; 17:343–349.PubMedCrossRefGoogle Scholar
  9. 9.
    Ohta K, Mizutani A, Kawakami A et al. Plexin: A novel neuronal cell surface molecule that mediates cell adhesion via a homophilic binding mechanism in the presence of calcium ions. Neuron 1995; 14:1189–1199.PubMedCrossRefGoogle Scholar
  10. 10.
    Ohta K, Takagi S, Asou H et al. Involvement of neuronal cell surface molecule B2 in the formation of retinal plexiform layers. Neuron 1992; 9:151–161.PubMedCrossRefGoogle Scholar
  11. I I.
    Takagi S, Hirata T, Agata K et al. The A5 antigen, a candidate for the neuronal recognition molecule, has homologies to complement component and coagulation factors. Neuron 1991; 7:295–307.PubMedCrossRefGoogle Scholar
  12. 12.
    Takagi S, Kasuya Y, Shimizu M et al. Expression of a cell adhesion molecule, neuropilin, in the developing chick nervous system. Dev Biol 1995; 170:207–222.PubMedCrossRefGoogle Scholar
  13. 13.
    Kawakami A, Kitsukawa T, Takagi S et al. Developmentally regulated expression of a cell surface protein, neuropilin, in the mouse nervous system. J Neurobiol 1996; 29:1–17.PubMedCrossRefGoogle Scholar
  14. 14.
    Chen H, Chedotal A, He Z et al. Neuropilin-2, a novel member of the neuropilin family, is a high affinity receptor for the semaphorins SemaE and SemaIV but not SemaIII. Neuron 1997; 19:547–559.PubMedCrossRefGoogle Scholar
  15. 15.
    Maestrini E, Tamagnone L, Longati P et al. A family of transmembrane proteins with homology to the MET-hepatocyte growth factor receptor. Proc Natl Acad Sci USA 1996; 93:674–678.PubMedCrossRefGoogle Scholar
  16. 16.
    Kameyama T, Murakami Y, Suto F et al. Identification of plexin family molecules in mice. Biochem Biophys Res Commun 1996; 226:396–402.PubMedCrossRefGoogle Scholar
  17. 17.
    Kameyama T, Murakami Y, Suto F et al. Identification of a neuronal cell surface molecule, plexin, in mice. Biochem Biophys Res Commun 1996; 226:524–529.PubMedCrossRefGoogle Scholar
  18. 18.
    Tamagnone L, Artigiani S, Chen H et al. Plexins are a large family of receptors for trans-membrane, secreted, and GPI-anchored semaphorins in vertebrates. Cell 1999; 99:71–80.PubMedCrossRefGoogle Scholar
  19. 19.
    Fujisawa H, Otsuki T, Takagi S et al. An aberrant retinal pathway and visual centers inXenopustadpoles share a common cell surface molecule, A5 antigen. Dev Biol 1989; 135:231–240.PubMedCrossRefGoogle Scholar
  20. 20.
    Kitsukawa T, Shimono A, Kawakami A et al. Overexpression of a membrane protein, neuropilin, in chimeric mice causes anomalies in the cardiovascular system, nervous system and limbs. Development 1995; 121:4309–4318.PubMedGoogle Scholar
  21. 21.
    Fujisawa H, Kitsukawa T, Kawakami A et al. Roles of a neuronal cell surface molecule, neuropilin, in nerve fiber fasciculation and guidance. Cell Tiss Res 1997; 290:465–470.CrossRefGoogle Scholar
  22. 22.
    Bagnard D, Lohrum M, Uziel D et al. Semaphorins act as attractive and repulsive guidance signals during the development of cortical projections. Development 1998; 125:5043–53.PubMedGoogle Scholar
  23. 23.
    Giger RJ, Urquhart ER, Gillespie SKH et al. Neuropilin-2 is a receptor for semaphorin IV: Insight into the structural basis of receptor function and specificity. Neuron 1998; 21:1079–1092.PubMedCrossRefGoogle Scholar
  24. 24.
    Nakamura F, Tanaka M, Takahashi T et al. Neuropilin-1 extracellular domains mediate semaphorin D/III-induced growth cone collapse. Neuron 1998; 21:1093–1100.PubMedCrossRefGoogle Scholar
  25. 25.
    Kitsukawa T, Shimizu M, Sanbo M et al. Neuropilin-semaphorin III/D-mediated chemorepulsive signals play a crucial role in peripheral nerve projection in mice. Neuron 1997; 19:995–1005.PubMedCrossRefGoogle Scholar
  26. 26.
    Fujisawa H, Kitsukawa T. Receptors for collapsin/semaphorins. Current Opinion in Neurobiology 1998; 8:587–592.PubMedCrossRefGoogle Scholar
  27. 27.
    Giger RJ, Cloutier JF, Sahay A et al. Neuropilin-2 is required in vivo for selective axon guidance responses to secreted semaphorins. Neuron 2000; 25:29–41.PubMedCrossRefGoogle Scholar
  28. 28.
    Chen H, Bagri A, Zupicich JA et al. Neuropilin-2 regulates the development of selective cranial and sensory nerves and hippocampal mossy fiber projections. Neuron 2000; 25:43–56.PubMedCrossRefGoogle Scholar
  29. 29.
    Campbell DS, Regan AG, Lopez JS et al. Semaphorin 3A elicits stage-dependent collapse, turning, and branching inXenopusretinal growth cones. J Neurosci 2001; 21:8538–8547.PubMedGoogle Scholar
  30. 30.
    Takahashi T, Fournier A, Nakamura F et al. Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors. Cell 1999; 99:59–69.PubMedCrossRefGoogle Scholar
  31. 31.
    Rohm B, Ottemeyer A, Lohrum M et al. Plexin/neuropilin complexes mediate repulsion by the axonal guidance signal scmaphorin 3A. Mech Dev 2000; 93:95–104.PubMedCrossRefGoogle Scholar
  32. 32.
    Murakami Y, Suto F, Shimizu M, et al. Differential expression of plexin-A subfamily members in the mouse nervous system. Dev Dyn 2001; 220:246–258.PubMedCrossRefGoogle Scholar
  33. 33.
    Soker S, Takashima S, Miao HQ et al. Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific receptor for vascular endothelial growth factor. Cell 1998; 92:735–745.PubMedCrossRefGoogle Scholar
  34. 34.
    Kawasaki T, Kitsukawa T, Bekku Y et al. A requirement for neuropilin-1 in embryonic vessel formation. Development 1999; 126:4885–4893.Google Scholar
  35. 35.
    Shimizu M, Murakami Y, Suto F et al. Determination of cell adhesion sites of neuropilin-l. J Cell Biol 2000; 148:1283–1294.PubMedCrossRefGoogle Scholar
  36. 36.
    Satoda M, Takagi S, Ohta K et al. Differential expression of two cell surface proteins, neuropilin and plexin, inXenopusolfactory axon subclasses. J Neurosci 1995; 15:942–955.PubMedGoogle Scholar
  37. 37.
    Kawasaki K, Bekku Y, Suto F et al. Requirement of neuropilin-l-mediated Sema3A signals in patterning of the sympathetic nervous system. Development 2002; 129:671–680.PubMedGoogle Scholar
  38. 38.
    Taniguchi M, Yuasa S, Fujisawa H et al. Disruption of scmaphorin III/D gene causes severe abnormality in peripheral nerve projection. Neuron 1997; 19:519–530.PubMedCrossRefGoogle Scholar
  39. 39.
    Castellani V, Chedotal A, Schachner M et al. Analysis of the LI-deficient mouse phenotype reveals cross-talk between Sema3A and LI signaling pathways in axonal guidance. Neuron 2000; 27:237–249.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  1. 1.Group of Developmental Neurobiology Division of Biological ScienceNagoya University Graduate School of ScienceChikusa-ku, NagoyaJapan

Personalised recommendations