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

Semaphorins are a targe family of secreted and transmembrane proteins, several of which are implicated in repulsive axon guidance. Neuropili n (neuropilin-1) was recently identified as a receptor for Collapsin-1 /Semaphorin III/D (Sema III). We report the identification of a relate d protein, neuropilin-2, whose mRNA is expressed by developing neurons in a pattern largely, though not comptetely, nonoverlapping with that of neuropilin-1. Unlike neuropilin-1, which binds with high affinity to the th ree structurally related semaphorins Sema III, Sema E, and S ema IV, neuropilin-2 shows high affinity binding only to Sema E and Se ma IV, not Sema III. These results identify neuropilins as a family of receptors (or components of receptors) for at least one semaphorin su bfamily. They also suggest that the specificity of action of different members of this subfamily may be determined by the complement of neur opilins expressed by responsive cells.