Pathfinding molecules branch out: Semaphorin family members regulate synapse development

Abstract

Although best known for their role guiding axons to their appropriate targets in the developing nervous system, semaphorin family members also play important roles in the immune system, developing vasculature, cardiac morphogenesis, and cancer. As semaphorins and their receptors are expressed at the correct time and place to mediate synapse development, it is perhaps not surprising that recent loss-of-function and gain-of-function studies demonstrate a role for semaphorins in modulating both synapse formation and function. The majority of semaphorin family members are membrane-associated proteins, suggesting the tantalizing possibility that semaphorins could signal both as a ligand and via their own intracellular domains to mediate synapse development. In this manner, semaphorin family members and their receptors could coordinate assembly of the pre- and postsynaptic specializations, potentially via a trans-synaptic signaling mechanism.