Neuropilin signalling in vessels, neurons and tumours

The neuropilins NRP1 and NRP2 are transmembrane proteins that regulate many different aspects of vascular and neural development. Even though they were originally identified as adhesion molecules, they are most commonly studied as co-receptors for secreted signalling molecules of the class 3 semaphorin (SEMA) and vascular endothelial growth factor (VEGF) families. During nervous system development, both classes of ligands control soma migration, axon patterning and synaptogenesis in the central nervous system, and they additionally help to guide the neural crest cell precursors of neurons and glia in the peripheral nervous system. Both classes of neuropilin ligands also control endothelial cell behaviour, with NRP1 acting as a VEGF-A isoform receptor in blood vascular endothelium and as a semaphorin receptor in lymphatic valve endothelium, and NRP2 promoting lymphatic vessel growth induced by VEGF-C. Here we provide an overview of neuropilin function in neurons and neural crest cells, discuss current knowledge of neuropilin signalling in the vasculature and conclude with a summary of neuropilin roles in cancer.

► Neuropilins bind most members of the class 3 semaphorins (SEMA) family. ► Neuropilins bind members of the vascular endothelial growth factor (VEGF) family. ► Neuropilin ligands regulate neuronal behaviour and guide neural crest cells. ► Neuropilin ligands control endothelial cell behaviour in blood/lymphatic vessels. ► Neuropilins promote cancer progression in multiple pathways.