Neuropilin-2 is a receptor for semaphorin IV: insight into the structural basis of receptor function and specificity

Neuron. 1998 Nov;21(5):1079-92. doi: 10.1016/s0896-6273(00)80625-x.


Neuropilins bind secreted members of the semaphorin family of proteins. Neuropilin-1 is a receptor for Sema III. Here, we show that neuropilin-2 is a receptor for the secreted semaphorin Sema IV and acts selectively to mediate repulsive guidance events in discrete populations of neurons. neuropilin-2 and semaIV are expressed in strikingly complementary patterns during neurodevelopment. The extracellular complement-binding (CUB) and coagulation factor domains of neuropilin-2 confer specificity to the Sema IV repulsive response, and these domains of neuropilin-1 are necessary and sufficient for binding of the Sema III semaphorin (sema) domain. The coagulation factor domains alone are necessary and sufficient for binding of the Sema III immunoglobulin- (Ig-) basic domain and the unrelated ligand, vascular endothelial growth factor (VEGF). Lastly, neuropilin-1 can homomultimerize and form heteromultimers with neuropilin-2. These results provide insight into how interactions between neuropilins and secreted semaphorins function to coordinate repulsive axon guidance during neurodevelopment.

Publication types

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

MeSH terms

  • Animals
  • Cells, Cultured
  • Coculture Techniques
  • Embryo, Mammalian
  • Ganglia, Spinal / cytology
  • Ganglia, Sympathetic / cytology
  • Glycoproteins / physiology
  • Humans
  • Nerve Growth Factors / metabolism*
  • Nerve Growth Factors / physiology
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / metabolism*
  • Nerve Tissue Proteins / physiology
  • Neurons / metabolism
  • Neuropilin-1
  • Rats
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / physiology*
  • Semaphorin-3A
  • Superior Cervical Ganglion / chemistry
  • Superior Cervical Ganglion / cytology


  • Glycoproteins
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Receptors, Cell Surface
  • Semaphorin-3A
  • semaphorin IV
  • Neuropilin-1