Neuropilins: a versatile partner of extracellular molecules that regulate development and disease

Neuropilins are a vertebrate-specific family of membrane multidomain proteins. They are crucial for the embryonic development of neural and vascular systems, whereas in the adult organism they are implicated in many processes, such as angiogenesis and the immune response. Additionally, it has been shown that they are overexpressed in numerous types of tumours, which results in higher microvessel density and correlates with poor prognosis. Their functions have been linked to their binding partners: semaphorins/collapsins, vascular endothelial growth factors (VEGFs), fibroblast growth factors (FGFs), hepatocyte growth factor/scatter factor and heparin/heparan sulfate (HS). Multiplicity of ligands alongside complex formation with several membrane receptors makes neuropilins potential 'hub' proteins, which act as a scaffold for multimeric associations. This review focuses on the structural features of neuropilins that underpin their multiple molecular interactions and hence their functions.