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Neuropilins as Semaphorin Receptors

In vivo Functions in Neuronal Cell Migration and Axon Guidance
  • Anil Bagri
  • Marc Tessier-Lavigne
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 515)

Abstract

After the initial discovery of neuropilin-1 as an epitope on axons recognized by a monoclonal antibody, neuropilins were rediscovered in the search for receptors mediating the repulsive actions of class 3 Semaphorins, notably Sema3A. Neuropilins are the ligand binding moieties in the class 3 Semaphorin receptor complexes, with the signaling moieties apparently provided by members of the plexin family. In their capacity as Semaphorin receptors, neuropilins have been shown to transduce repulsive guidance signals that direct a large variety of cell migration and axon guidance events. We summarize their demonstrated roles in driving axon fasciculation, channeling various axonal populations, inhibiting axonal branching, creating exclusion zones for axons, and providing directional guidance cues by being presented in gradients. In addition to their roles in repulsive axon guidance, evidence is accumulating that neuropilins also transduce some attractive guidance functions of Semaphorins.

Keywords

Olfactory Bulb Growth Cone Floor Plate Exclusion Zone Sensory Axon 
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.

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References

  1. 1.
    Kolodkin AL, Matthes DJ, O’Connor TP et al. Fasciclin IV: Sequence, expression, and function during growth cone guidance in the grasshopper embryo. Neuron 1992; 9:831–845.PubMedCrossRefGoogle Scholar
  2. 2.
    Kolodkin AL, Matthes DJ, Goodman CS. The semaphorin genes encode a family of trans-membrane and secreted growth cone guidance molecules. Cell 1993; 75:1389–1199.PubMedCrossRefGoogle Scholar
  3. 3.
    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
  4. 4.
    Puschel AW, Adams RH, Betz H. Murine semaphorin D/collapsin is a member of a diverse gene family and creates domains inhibitory for axonal extension. Neuron 1995; 14:941–948.PubMedCrossRefGoogle Scholar
  5. 5.
    Luo Y, Shepherd I, Li J et al. A family of molecules related to collapsin in the embryonic chick nervous system. Neuron 1995; 14:1131–1140.PubMedCrossRefGoogle Scholar
  6. 6.
    Adams RH, Betz H, Puschel AW. A novel class of murine semaphorins with homology to thrombospondin is differentially expressed during early embryogenesis. Mech Dev 1996; 57:33–45.PubMedCrossRefGoogle Scholar
  7. 7.
    Matthes DJ, Sink H, Kolodkin AL et al. Semaphorin II can function as a selective inhibitor of specific synaptic arborizations. Cell 1995; 81:631–639.PubMedCrossRefGoogle Scholar
  8. 8.
    Winberg ML, Noordermeer JN, Tamagnone L et al. Plexin A is a neuronal semaphorin receptor that controls axon guidance. Cell 1998; 95:903–916.PubMedCrossRefGoogle Scholar
  9. 9.
    Messersmith EK, Leonardo ED, Shatz CJ et al. Semaphorin III can function as a selective chemorepellent to pattern sensory projections in the spinal cord. Neuron 1995; 14:949–959.PubMedCrossRefGoogle Scholar
  10. 10.
    Varela-Echavarria A, Tucker A, Puschel AW et al. Motor axon subpopulations respond differentially to the chemorepellents netrin-1 and semaphorin D. Neuron 1997; 18:193–207.PubMedCrossRefGoogle Scholar
  11. 11.
    Kobayashi H, Koppel AM, Luo Y et al. A role for collapsin-1 in olfactory and cranial sensory axon guidance. J Neurosci 1997; 17:8339–8352.PubMedGoogle Scholar
  12. 12.
    Bagnard D, Lohrum M, Uziel D et al. Semaphorins act as attractive and repulsive guidance signals during the development of cortical projections. Development 1998; 125:5043–5053.PubMedGoogle Scholar
  13. 13.
    Chedotal A, Del Rio JA, Ruiz M et al. Semaphorins III and IV repel hippocampal axons via two distinct receptors. Development 1998; 125:4313–4323.PubMedGoogle Scholar
  14. 14.
    Rabacchi SA, Solowska JM, Kruk B et al. Collapsin-l/semaphorin-III/D is regulated developmentally in Purkinje cells and collapses pontocerebellar mossy fiber neuronal growth cones. J Neurosci 1999; 19:4437–4448.PubMedGoogle Scholar
  15. 15.
    He Z, Tessier-Lavigne M. Neuropilin is a receptor for the axonal chemorepellent Semaphorin III. Cell 1997; 90:739–751.PubMedCrossRefGoogle Scholar
  16. 16.
    Kolodkin AL, Levengood DV, Rowe EG et al. Neuropilin is a semaphorin III receptor. Cell 1997; 90:753–762.PubMedCrossRefGoogle Scholar
  17. 17.
    Feiner L, Koppel AM, Kobayashi H et al. Secreted chick semaphorins bind recombinant neuropilin with similar affinities but bind different subsets of neurons in situ. Neuron 1997; 19:539–545.PubMedCrossRefGoogle Scholar
  18. 18.
    Takahashi T, Nakamura F, Strittmatter SM. Neuronal and non-neuronal collapsin-1 binding sites in developing chick are distinct from other semaphorin binding sites. J Neurosci 1997; 17:9183–9193.PubMedGoogle Scholar
  19. 19.
    Eickholt BJ, Morrow R, Walsh FS et al. Structural features of collapsin required for biological activity and distribution of binding sites in the developing chick. Mol Cell Neurosci 1997; 9:358–371.PubMedCrossRefGoogle Scholar
  20. 20.
    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
  21. 21.
    Taniguchi M, Yuasa S, Fujisawa H et al. Disruption of semaphorin III/D gene causes severe abnormality in peripheral nerve projection. Neuron 1997; 19:519–530.PubMedCrossRefGoogle Scholar
  22. 22.
    Koppel AM, Feiner L, Kobayashi H et al. A 70 amino acid region within the semaphorin domain activates specific cellular response of semaphorin family members. Neuron 1997; 19:531–537.PubMedCrossRefGoogle Scholar
  23. 23.
    Giger RJ, Pasterkamp RJ, Holtmaat AJ et al. Semaphorin III: role in neuronal development and structural plasticity. Prog Brain Res 1998; 117:133–149.PubMedCrossRefGoogle Scholar
  24. 24.
    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 Sema E and Sema IV but not Sema III. Neuron 1997; 19:547–559.Google Scholar
  25. 25.
    Giger RJ, Urquhart ER, Gillespie SK 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
  26. 26.
    Chen H, He Z, Bagri A et al. Semaphorin-neuropilin interactions underlying sympathetic axon responses to class III semaphorins. Neuron 1998; 21:1283–1290.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.
    Takahashi T, Nakamura F, Jin Z et al. Semaphorins A and E act as antagonists of neuropilin1 and agonists of neuropilin-2 receptors. Nat Neurosci 1998; 1:487–493.PubMedCrossRefGoogle Scholar
  30. 30.
    Koppel AM, Raper JA. Collapsin-1 covalently dimerizes, and dimerization is necessary for collapsing activity. J Biol Chem 1998; 273:15708–15713.PubMedCrossRefGoogle Scholar
  31. 31.
    Klostermann A, Lohrum M, Adams RH et al. The chemorepulsive activity of the axonal guidance signal semaphorin D requires dimerization. J Biol Chem 1998; 273:7326–7331.PubMedCrossRefGoogle Scholar
  32. 32.
    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
  33. 33.
    Takahashi T, Fournier A, Nakamura F et al. Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors. Cell 1999; 99:59–69.PubMedCrossRefGoogle Scholar
  34. 34.
    Takahashi T, Strittmatter SM. Plexinal autoinhibition by the plexin sema domain. Neuron 2001; 29:429–439.PubMedCrossRefGoogle Scholar
  35. 35.
    Rohm B, Ottemeyer A, Lohrum M et al. Plexin/neuropilin complexes mediate repulsion by the axonal guidance signal semaphorin 3A. Mech Dev 2000; 93:95–104.PubMedCrossRefGoogle Scholar
  36. 36.
    Cheng HJ, Bagri A, Yaron A et al. Plexin-A3 mediates semaphorin signaling and regulates the development of hippocampal axonal projections. Neuron 2001; 32:249–263.Google Scholar
  37. 37.
    Tessier-Lavigne M. Eph receptor tyrosine kinases, axon repulsion, and the development of topographic maps. Cell 1995; 82:345–348.PubMedCrossRefGoogle Scholar
  38. 38.
    Keynes R, Tannahill D, Morgenstern DA et al. Surround repulsion of spinal sensory axons in higher vertebrate embryos. Neuron 1997; 18:889–897.PubMedCrossRefGoogle Scholar
  39. 39.
    Cloutier JF, Giger RJ, Koentges G et al. Neuropilin-2 mediates axonal fasciculation, zonal segregation, but not axonal convergence, of primary accessory olfactory neurons. Neuron 2002; 33:877–892.PubMedCrossRefGoogle Scholar
  40. 40.
    Bagnard D, Chounlamountri N, Puschel AW et al. Axonal surface molecules act in combination with semaphorin 3a during the establishment of corticothalamic projections. Cereb Cortex 2001; 11:278–285.PubMedCrossRefGoogle Scholar
  41. 41.
    Fu SY, Sharma K, Luo Y et al. SEMA3A regulates developing sensory projections in the chicken spinal cord. J Neurobiol 2000; 45:227–236.PubMedCrossRefGoogle Scholar
  42. 42.
    Puschel AW, Adams RH, Betz H. The sensory innervation of the mouse spinal cord may be patterned by differential expression of and differential responsiveness to semaphorins. Mol Cell Neurosci 1996; 7:419–431.PubMedCrossRefGoogle Scholar
  43. 43.
    Behar 0, Golden JA, Mashimo H et al. Semaphorin III is needed for normal patterning and growth of nerves, bones and heart. Nature 1996; 383:525–528.PubMedCrossRefGoogle Scholar
  44. 44.
    Renzi MJ, Wexler TL, Raper JA. Olfactory sensory axons expressing a dominant-negative semaphorin receptor enter the CNS early and overshoot their target. Neuron 2000; 28:437–447.PubMedCrossRefGoogle Scholar
  45. 45.
    Zou Y, Stoeckli E, Chen H et al. Squeezing axons out of the gray matter: A role for slit and semaphorin proteins from midline and ventral spinal cord. Cell 2000; 102:363–375.PubMedCrossRefGoogle Scholar
  46. 46.
    Henke-Fahle S, Beck KW, Puschel AW. Differential responsiveness to the chemorepellent Semaphorin 3A distinguishes ipsi-and contralaterally projecting axons in the chick mid-brain. Dev Biol 2001; 237:381–397.PubMedCrossRefGoogle Scholar
  47. 47.
    Marin 0, Yaron A, Bagri A et al. Sorting of striatal and cortical interneurons regulated by semaphorin-neuropilin interactions. Science 2001; 293:872–875.PubMedCrossRefGoogle Scholar
  48. 48.
    Polleux F, Giger RJ, Ginty DD et al. Patterning of cortical efferent projections by semaphorinneuropilin interactions. Science 1998; 282:1904–1906.PubMedCrossRefGoogle Scholar
  49. 49.
    Bagnard D, Thomasset N, Lohrum M et al. Spatial distributions of guidance molecules regulate chemorepulsion and chemoattraction of growth cones. J Neurosci 2000; 20:1030–1035.PubMedGoogle Scholar
  50. 50.
    Sugimoto Y, Taniguchi M, Yagi T et al. Guidance of glial precursor cell migration by secreted cues in the developing optic nerve. Development 2001; 128:3321–3330.PubMedGoogle Scholar
  51. 51.
    de Castro F, Hu L, Drabkin H et al. Chemoattraction and chemorepulsion of olfactory bulb axons by different secreted semaphorins. J Neurosci 1999; 19:4428–4436.PubMedGoogle Scholar
  52. 52.
    Song H, Ming G, He Z et al. Conversion of neuronal growth cone responses from repulsion to attraction by cyclic nucleotides. Science 1998; 281:1515–1518.PubMedCrossRefGoogle Scholar
  53. 53.
    Polleux F, Morrow T, Ghosh A. Semaphorin 3A is a chemoattractant for cortical apical dendrites. Nature 2000; 404:567–573.PubMedCrossRefGoogle Scholar
  54. 54.
    Nakamura F, Kalb RG, Strittmatter SM. Molecular basis of semaphorin-mediated axon guidance. J Neurobiol 2000; 44:219–229.PubMedCrossRefGoogle Scholar
  55. 55.
    Nakamura F, Tanaka M, Takahashi T et al. Neuropilin-1 extracellular domains mediate semaphorin D/111-induced growth cone collapse. Neuron 1998; 21:1093–1100.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Anil Bagri
    • 1
  • Marc Tessier-Lavigne
    • 2
  1. 1.Department of Anatomy and of Biochemistry and Biophysics, Howard Hughes Medical InstituteUniversity of CaliforniaSan FranciscoUSA
  2. 2.Department of Biological Sciences, Howard Hughes Medical InstituteStanford UniversityStanfordUSA

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