Neuropilin Is a Semaphorin III Receptor

TLDR

The semaphorin family includes proteins that mediate repulsive axon guidance, and Sema III is known to collapse growth cones and guide sensory afferents, but its receptor mechanism remains unclear. We identify neuropilin as a Sema III receptor and show that neuropilin‑2, a related family member, binds Sema III and is expressed in distinct neuronal populations in the rat embryonic nervous system.

Abstract

The semaphorin family contains a large number of phylogenetically conserved proteins and includes several members that have been shown to function in repulsive axon guidance. Semaphorin III (Sema III) is a secreted protein that in vitro causes neuronal growth cone collapse and chemorepulsion of neurites, and in vivo is required for correct sensory afferent innervation and other aspects of development. The mechanism of Sema III function, however, is unknown. Here, we report that neuropilin, a type I transmembrane protein implicated in aspects of neurodevelopment, is a Sema III receptor. We also describe the identification of neuropilin-2, a related neuropilin family member, and show that neuropilin and neuropilin-2 are expressed in overlapping, yet distinct, populations of neurons in the rat embryonic nervous system.