Neuropilin-1 extracellular domains mediate semaphorin D/III-induced growth cone collapse

Neuron. 1998 Nov;21(5):1093-100. doi: 10.1016/s0896-6273(00)80626-1.


Somatosensory axon outgrowth is repulsed when soluble semaphorin D (semD) binds to growth cone neuropilin-1 (Npn-1). Here, semD ligand binding studies of Npn-1 mutants demonstrate that the sema domain binds to the amino-terminal quarter, or complement-binding (CUB) domain, of Npn-1. By herpes simplex virus- (HSV-) mediated expression of Npn-1 mutants in chick retinal ganglion cells, we show that semD-induced growth cone collapse requires two segments of the ectodomain of Npn-1, the CUB domain and the juxtamembrane portion, or MAM (meprin, A5, mu) domain. In contrast, the transmembrane segment and cytoplasmic tail of Npn-1 are not required for biologic activity. These data imply that the CUB and MAM ectodomains of Npn-1 interact with another transmembrane growth cone protein that in turn transduces a semD signal into axon repulsion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cells, Cultured
  • Chick Embryo
  • Extracellular Space / physiology*
  • Glycoproteins / genetics
  • Glycoproteins / pharmacology*
  • Growth Cones / physiology*
  • Humans
  • Mice
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Neuropilin-1
  • Peptide Fragments / physiology
  • Protein Binding
  • Protein Structure, Tertiary
  • Retinal Ganglion Cells / cytology
  • Semaphorin-3A


  • Glycoproteins
  • Nerve Tissue Proteins
  • Peptide Fragments
  • Semaphorin-3A
  • Neuropilin-1