nature neuroscience • volume 1 no 6 • october 1998 439 also focused attention on potential interacting partners for semaphorins and neuropilins. First, neuropilins have, rather surprisingly, been found also to be high-affinity receptors for a particular isoform of vascular endothelial cell growth factor, and to enhance binding of this ligand to its signaling receptor, the receptor tyrosine kinase KDR/Flk1, on endothelial cells15. This has raised the interesting possibility that other receptor tyrosine kinases might function as co-receptors with neuropilins on neurons as well. In addition, a recent study has identified a novel semaphorin receptor that mediates the responses of human monocytes to two virally derived semaphorins (which are distantly related to animal semaphorins)16, and which is a member of the plexin family of transmembrane proteins17,18. Because many plexin members are expressed in the nervous system during development17,18, it will be of interest to determine whether other plexins function as co-receptors for neuropilins, or as receptors for semaphorins in the other five classes (as none of those so far tested seem to bind neuropilins2,13,19). Such studies are likely to help elucidate the complete molecular composition of class III semaphorin receptors, and thereby to pave the way for an understanding of how a semaphorin signal is transduced into the cytoskeletal changes that underlie growth-cone repulsion and collapse.