| Semaphorin | |
|---|---|
| Identifiers | |
| Symbol | Semaphorin |
| InterPro | IPR027231 |
| CDD | cd04979 |
| Membranome | 71 |
Semaphorins are a class of secreted and membraneproteins that were originally identified asaxonalgrowth cone guidance molecules. They primarily act as short-range inhibitory signals and signal through multimericreceptor complexes.[1][2] Semaphorins are usually cues to deflect axons from inappropriate regions, especially important in theneural system development. The major class of proteins that act as their receptors are calledplexins, withneuropilins as their co-receptors in many cases. The main receptors for semaphorins are plexins, which have established roles in regulating Rho-familyGTPases. Recent work shows that plexins can also influenceR-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.
Every semaphorin is characterised by the expression of a specific region of about 500 amino acids called thesema domain.
Semaphorins were named after the English wordSemaphore, which originated from Greek, meaningsign-bearer.[3]
The Semaphorins are grouped into eight major classes based on structure andphylogenetic tree analyses.[4] The first seven are ordered by number, from class 1 to class 7. The eighth group is class V, where V stands forvirus. Classes 1 and 2 are found in invertebrates only, whilst classes 3, 4, 6, and 7 are found in vertebrates only. Class 5 is found in both vertebrates and invertebrates, and class V is specific to viruses.
Classes 1 and 6 are considered to be homologues of each other; they are each membrane bound in invertebrates and vertebrates, respectively. The same applies to classes 2 and 3; they are both secreted proteins specific to their respectivetaxa.
Each class of Semaphorin has many subgroups of different molecules that share similar characteristics. For example, Class 3 Semaphorins range from SEMA3A to SEMA3G.
In humans, the genes are:
Different semaphorins use different types of receptors:
Semaphorins are versatile ligands. Their discovery was in regards to axon guidance in the limb buds of grasshoppers in 1992, but since then, it has been discovered that semaphorins have a role in many processes. They not only guide axons in development, but also have major roles in immune function (classes 4, 6, and 7) and the development of bones. Class 3 semaphorins are one of the most versatile semaphorin classes, in which Sema3a is the most studied.
During development, semaphorins and their receptors may be involved in the sorting of pools of motor neurons and the modulation of pathfinding for afferent and efferent axons from and to these pools.[6] For instance, Sema3a repels axons from the dorsal root ganglia, facial nerves, vagal nerves, olfactory-sensory, cortical nerves, hippocampal nerves and cerebellar nerves.
Class 3 semaphorins have an important function after traumaticcentral nervous system injuries, such asspinal cord injury. They regulate neuronal and non-neuronal cells associated with the traumatic injury due to their presence in the scar tissue. Class 3 semaphorins modulateaxonal regrowth,re-vascularisation,re-myelination and theimmune response after central nervous system trauma.[7]