Semaphorins are a class of secreted and membrane proteins that were originally identified as axonal growth cone guidance molecules. They primarily act as short-range inhibitory signals and signal through multimeric receptor complexes. Semaphorins are usually cues to deflect axons from inappropriate regions, especially important in the neural system development. The major class of proteins that act as their receptors are called plexins, with neuropilins as their co-receptors in many cases. The main receptors for semaphorins are plexins, which have established roles in regulating Rho-family GTPases. Recent work shows that plexins can also influence R-Ras, which, in turn, can regulate integrins. Such regulation is probably a common feature of semaphorin signalling and contributes substantially to our understanding of semaphorin biology.
A plexin is a protein which acts as a receptor for semaphorin family signaling proteins. It is classically known for its expression on the surface of axon growth cones and involvement in signal transduction to steer axon growth away from the source of semaphorin. Plexin also has implications in development of other body systems by activating GTPase enzymes to induce a number of intracellular biochemical changes leading to a variety of downstream effects.
Neuropilin 2 (NRP2) is a protein that in humans is encoded by the NRP2 gene.
Neuropilin-1 is a protein that in humans is encoded by the NRP1 gene. In humans, the neuropilin 1 gene is located at 10p11.22. This is one of two human neuropilins.
Semaphorin-3A is a protein that in humans is encoded by the SEMA3A gene.
Semaphorin-4D (SEMA4D) also known as Cluster of Differentiation 100 (CD100), is a protein of the semaphorin family that in humans is encoded by the SEMA4D gene.
RNA-binding protein 5 is a protein that in humans is encoded by the RBM5 gene.
Zinc finger MYND domain-containing protein 10 is a protein that in humans is encoded by the ZMYND10 gene.
Semaphorin-3B is a protein that in humans is encoded by the SEMA3B gene.
Semaphorin-3C is a protein that in humans is encoded by the SEMA3C gene.
Sodium-coupled neutral amino acid transporter 3 is a protein that in humans is encoded by the SLC38A3 gene.
Plexin-A1 is a protein that in humans is encoded by the PLXNA1 gene.
Semaphorin 7A, GPI membrane anchor (SEMA7A) also known as CD108, is a human gene.
Aminoacylase-1 is an enzyme that in humans is encoded by the ACY1 gene.
Plexin-A2 is a protein that in humans is coded by the PLXNA2 gene.
Semaphorin-4A is a protein that in humans is encoded by the SEMA4A gene.
RNA-binding protein 6 is a protein that in humans is encoded by the RBM6 gene. RBM6 orthologs have been identified in all mammals for which complete genome data are available.
Semaphorin-4B is a protein that in humans is encoded by the SEMA4B gene.
Plexin-A4 is a protein that in humans is encoded by the PLXNA4 gene.
The growth cone is a highly dynamic structure of the developing neuron, changing directionality in response to different secreted and contact-dependent guidance cues; it navigates through the developing nervous system in search of its target. The migration of the growth cone is mediated through the interaction of numerous trophic and tropic factors; netrins, slits, ephrins and semaphorins are four well-studied tropic cues (Fig.1). The growth cone is capable of modifying its sensitivity to these guidance molecules as it migrates to its target; this sensitivity regulation is an important theme seen throughout development.
