Semaphorin-neuropilin interactions underlying sympathetic axon responses to class III semaphorins

Neuropilin-1 and neuropilin-2 show specificity in binding to different clas s III semaphorins, including Sema III, Sema E, and Sema IV, suggesting that the specificity of action of these semaphorins is dictated by the compleme nt of neuropilins expressed by responsive neurons. In support of this, we s how that sympathetic axons coexpress neuropilin-1 and -2, that their respon ses to Sema III, Sema E, and Sema IV are affected in predicted ways by anti bodies to neuropilin-1, and that neuropilin-1 and -2 can form homo- and het erooligomers through an interaction involving at least partly the neuropili n MAM (meprin, A5, mu) domain. These results support the idea that in sympa thetic axons, the Sema III signal is mediated predominantly by neuropilin-1 oligomers, the Sema IV signal by neuropilin-2 oligomers, and the Sema E si gnal by neuropilin-1 and -2, either as homo- or heterooligomers.