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{{Pfam_box
⚫
'''Semaphorins''' are a class of secreted and membrane [[protein]]s that act as [[axonal]] [[growth cone]] guidance molecules. They primarily act as short-range inhibitory signals and signal through multimeric [[receptor (biochemistry)|receptor]] complexes. They are usually cues to deflect axons from inappropriate regions, especially important in [[nervous system|neural system]] development. The major class of proteins that act as their receptors are called [[plexin]]s. The main receptors for semaphorins are plexins, which have established roles in regulating Rho-family [[GTPases]]. Recent work shows that plexins can also influence [[RRAS|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.
| Symbol = Semaphorin
| Name = Semaphorin
| image =
| width =
| caption =
| InterPro= IPR027231
| SMART=
| PROSITE =
| SCOP =
| TCDB =
| OPM family=
| OPM protein=
| Pfam=
| PDB=
| Membranome superfamily= 71
| CDD = cd04979
}}

⚫
'''Semaphorins''' are a class of secreted and membrane [[protein]]s that were originally identified as [[axonal]] [[growth cone]] guidance molecules. They primarily act as short-range inhibitory signals and signal through multimeric [[receptor (biochemistry)|receptor]] complexes.<ref name="pmid27397516 ">{{cite journal |vauthors=Kong Y, Janssen BJ, Malinauskas T, Vangoor VR, Coles CH, Kaufmann R, Ni T, Gilbert RJ, Padilla-Parra S, Pasterkamp RJ, Jones EY |title=Structural Basis for Plexin Activation and Regulation |journal=Neuron |volume=91 |issue=8 |pages=1–13 |year=2016 |pmid=27397516 |pmc=4980550 |doi=10.1016/j.neuron.2016.06.018}}</ref><ref name="pmid23104057">{{cite journal |vauthors=Janssen BJ, Malinauskas T, Weir GA, Cader MZ, Siebold C, Jones EY |title=Neuropilins lock secreted semaphorins onto plexins in a ternary signaling complex |journal=Nature Structural & Molecular Biology |volume=19 |issue=12 |pages=1293–1299 |year=2012 |pmid=23104057 |doi=10.1038/nsmb.2416 |pmc=3590443}}</ref> Semaphorins are usually cues to deflect axons from inappropriate regions, especially important in the [[nervous system|neural system]] development. The major class of proteins that act as their receptors are called [[plexin]]s, with [[Neuropilin|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 [[RRAS|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.


Every semaphorin is characterised by the expression of a specific region of about 500 amino acids called the [[sema domain]].
Every semaphorin is characterised by the expression of a specific region of about 500 amino acids called the [[sema domain]].


Semaphorins were named after the English word ''[[Semaphore]]'', which originated from Greek, meaning ''sign-bearer''.
Semaphorins were named after the English word ''[[Semaphore]]'', which originated from Greek, meaning ''sign-bearer''.<ref>{{Cite journal|last1=Kolodkin|first1=Alex L.|last2=Matthes|first2=David J.|last3=Goodman|first3=Corey S.|date=31 December 1993|title=The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules|url=https://linkinghub.elsevier.com/retrieve/pii/009286749390625Z|journal=Cell|language=en|volume=75|issue=7|pages=1389–1399|doi=10.1016/0092-8674(93)90625-Z|pmid=8269517 |s2cid=21047504 }}</ref>


== Classes ==
== Classes ==
The Semaphorins are grouped into eight major classes based on structure and [[phylogenetic tree]] analyses.<ref name=pmid10367884>{{cite journal|author=Semaphorin Nomenclature Committee|title=Unified nomenclature for the Semaphorins/Collapsins|date=May 1999|doi=10.1016/S0092-8674(00)80766-7|pmid=10367884|url=http://www.sciencedirect.com/science/article/pii/S0092867400807667|journal=Cell|volume=97|issue=5|pages=551–552}}</ref> The first seven are ordered by number, from class 1 to class 7. The eighth group is class V, where V stands for [[virus]]. 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.
The Semaphorins are grouped into eight major classes based on structure and [[phylogenetic tree]] analyses.<ref name=pmid10367884>{{cite journal | vauthors = ((Semaphorin Nomenclature Committee)) | title = Unified nomenclature for the semaphorins/collapsins | journal = Cell | volume = 97 | issue = 5 | pages = 551–2 | date = May 1999 | pmid = 10367884 | doi = 10.1016/S0092-8674(00)80766-7 | doi-access = free }}</ref> The first seven are ordered by number, from class 1 to class 7. The eighth group is class V, where V stands for [[virus]]. 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 respective [[taxon|taxa]].
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 respective [[taxon|taxa]].


Each class of Semaphorin has many subgroups of different molecules that share similar characteristics. For example, Class 3 Semaphorins range from Sema3a to Sema3g.
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:
In humans, the genes are:
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* Most Semaphorins use receptors in the group of proteins known as [[plexins]].
* Most Semaphorins use receptors in the group of proteins known as [[plexins]].
* Class 3 semaphorins signal through heterocomplexes of [[neuropilin]]s, Class A Plexins, and cell adhesion molecules, and the makeup of these complexes likely provides specificity for binding and transducing signals from different Class 3 Semaphorins.<ref>{{cite journal|author=Sharma, A, Verhaagen, J, Harvey, AR|title=Receptor complexes for each of the Class 3 Semaphorins|journal=Front Cell Neurosci|date=July 2012|volume=6|doi=10.3389/fncel.2012.00028|url=http://www.frontiersin.org/Cellular_Neuroscience/10.3389/fncel.2012.00028/abstract}}</ref>
* Class 3 semaphorins signal through heterocomplexes of [[neuropilin]]s, [[Plexin#Classes|Class A Plexins]], and cell adhesion molecules, and the makeup of these complexes likely provides specificity for binding and transducing signals from different Class 3 Semaphorins.<ref>{{cite journal | vauthors = Sharma A, Verhaagen J, Harvey AR | title = Receptor complexes for each of the Class 3 Semaphorins | journal = Frontiers in Cellular Neuroscience | volume = 6 | pages = 28 | date = July 2012 | pmid = 22783168 | doi = 10.3389/fncel.2012.00028 | pmc=3389612| doi-access = free }}</ref>
* Class 7 Semaphorin are thought to use [[integrins]] as their receptors.
* Class 7 Semaphorin are thought to use [[integrins]] as their receptors.

⚫
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.<ref name="pmid15869472 ">{{cite journal |author= Cohen S, Funkelstein L, Livet J, Rougon G, Henderson CE, Castellani V, Mann F |journal= Eur J Neurosci |volume=21 |issue=7|pages=1767–76 |date=Apr 2005 |pmid= 15869472 |doi=10.1111/j.1460-9568.2005.04021.x |url= http://scivee.tv/node/3918 |title= A semaphorin code defines subpopulations of spinal motor neurons during mouse development}}</ref>


== Functions ==
== Functions ==
⚫
Semaphorins are very versatile. 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. One of the most versatile semaphorin classes is number 3, and specifically Sema3a.


[[File:Class III semaphorins in spinal cord injury.jpg|thumb|Class III semaphorins regulate multiple processes after spinal cord injury by influencing neuronal and non-neuronal cells. Copyright © 2014 Mecollari, Nieuwenhuis and Verhaagen. A perspective on the role of class III semaphorin signaling in central nervous system trauma. 1–17. doi: 10.3389/fncel.2014.00328]]
Sema3a repels axons from the dorsal root ganglia, facial nerves, vagal nerves, olfactory-sensory, cortical nerves, hippocampal nerves and cerebellar nerves.


⚫
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.
⚫
== External links ==

⚫
* {{MeshName|Semaphorins}}
⚫
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.<ref name="pmid15869472">{{cite journal | vauthors = Cohen S, Funkelstein L, Livet J, Rougon G, Henderson CE, Castellani V, Mann F | title = A semaphorin code defines subpopulations of spinal motor neurons during mouse development | journal = The European Journal of Neuroscience | volume = 21 | issue = 7 | pages = 1767–76 | date = April 2005 | pmid = 15869472 | doi = 10.1111/j.1460-9568.2005.04021.x | s2cid = 24049774 }}</ref> 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 traumatic [[central nervous system]] injuries, such as [[spinal 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 modulate [[axon]]al regrowth, [[Revascularization|re-vascularisation]], [[Remyelination|re-myelination]] and the [[immune response]] after central nervous system trauma.<ref>{{cite journal | vauthors = Mecollari V, Nieuwenhuis B, Verhaagen J | title = A perspective on the role of class III semaphorin signaling in central nervous system trauma | journal = Frontiers in Cellular Neuroscience | volume = 8 | pages = 328 | date = 2014 | pmid = 25386118 | pmc = 4209881 | doi = 10.3389/fncel.2014.00328 | doi-access = free }}</ref>


==Notes==
==Notes==
<references />
<references />


⚫
== External links ==
⚫
* {{MeshName|Semaphorins}}
{{Intercellular signaling peptides and proteins}}
{{Intercellular signaling peptides and proteins}}


[[Category:Proteins]]
[[Category:Single-pass transmembrane proteins]]

Latest revision as of 07:16, 16 August 2023

Semaphorin
Identifiers
SymbolSemaphorin
InterProIPR027231
CDDcd04979
Membranome71

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.[1][2] 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.

Every semaphorin is characterised by the expression of a specific region of about 500 amino acids called the sema domain.

Semaphorins were named after the English word Semaphore, which originated from Greek, meaning sign-bearer.[3]

Classes

[edit]

The Semaphorins are grouped into eight major classes based on structure and phylogenetic 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 for virus. 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 respective taxa.

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:

Semaphorin receptors

[edit]

Different semaphorins use different types of receptors:

  • Most Semaphorins use receptors in the group of proteins known as plexins.
  • Class 3 semaphorins signal through heterocomplexes of neuropilins, Class A Plexins, and cell adhesion molecules, and the makeup of these complexes likely provides specificity for binding and transducing signals from different Class 3 Semaphorins.[5]
  • Class 7 Semaphorin are thought to use integrins as their receptors.

Functions

[edit]
Class III semaphorins regulate multiple processes after spinal cord injury by influencing neuronal and non-neuronal cells. Copyright © 2014 Mecollari, Nieuwenhuis and Verhaagen. A perspective on the role of class III semaphorin signaling in central nervous system trauma. 1–17. doi: 10.3389/fncel.2014.00328

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 traumatic central nervous system injuries, such as spinal 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 modulate axonal regrowth, re-vascularisation, re-myelination and the immune response after central nervous system trauma.[7]

Notes

[edit]
  1. ^ Kong Y, Janssen BJ, Malinauskas T, Vangoor VR, Coles CH, Kaufmann R, Ni T, Gilbert RJ, Padilla-Parra S, Pasterkamp RJ, Jones EY (2016). "Structural Basis for Plexin Activation and Regulation". Neuron. 91 (8): 1–13. doi:10.1016/j.neuron.2016.06.018. PMC 4980550. PMID 27397516.
  2. ^ Janssen BJ, Malinauskas T, Weir GA, Cader MZ, Siebold C, Jones EY (2012). "Neuropilins lock secreted semaphorins onto plexins in a ternary signaling complex". Nature Structural & Molecular Biology. 19 (12): 1293–1299. doi:10.1038/nsmb.2416. PMC 3590443. PMID 23104057.
  3. ^ Kolodkin, Alex L.; Matthes, David J.; Goodman, Corey S. (31 December 1993). "The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules". Cell. 75 (7): 1389–1399. doi:10.1016/0092-8674(93)90625-Z. PMID 8269517. S2CID 21047504.
  4. ^ Semaphorin Nomenclature Committee (May 1999). "Unified nomenclature for the semaphorins/collapsins". Cell. 97 (5): 551–2. doi:10.1016/S0092-8674(00)80766-7. PMID 10367884.
  5. ^ Sharma A, Verhaagen J, Harvey AR (July 2012). "Receptor complexes for each of the Class 3 Semaphorins". Frontiers in Cellular Neuroscience. 6: 28. doi:10.3389/fncel.2012.00028. PMC 3389612. PMID 22783168.
  6. ^ Cohen S, Funkelstein L, Livet J, Rougon G, Henderson CE, Castellani V, Mann F (April 2005). "A semaphorin code defines subpopulations of spinal motor neurons during mouse development". The European Journal of Neuroscience. 21 (7): 1767–76. doi:10.1111/j.1460-9568.2005.04021.x. PMID 15869472. S2CID 24049774.
  7. ^ Mecollari V, Nieuwenhuis B, Verhaagen J (2014). "A perspective on the role of class III semaphorin signaling in central nervous system trauma". Frontiers in Cellular Neuroscience. 8: 328. doi:10.3389/fncel.2014.00328. PMC 4209881. PMID 25386118.
[edit]
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