Semaphorin

Function

Semaphorin (SEMA) are membrane proteins which act as axonal growth guidance molecules. SEMA act as short-range inhibitory signal^[1]. SEMA and Plexin are crucial for the development and homeostasis of nervous, immune and cardiovascular systems. There are 8 classes of SEMA numbered 1 to 7 and V (viral). Each class has several subgroups which share similar characteristics.

Semaphorin 3 is needed for normal patterning and growth of nerves, bones and heart^[2].
Semaphorin 4D acts through its receptor to tip the balance of bone homeostasis toward resorption ^[3].
Semaphorin 6D is part of the complex involved in macrophage polarization ^[4].
Semaphorin 7A promotes axon growth through integrins and MAPKs ^[5].

Relevance

SEMAs ar implicated in a number of developmental, psychiatric and neurodegenerative disorders^[6]. SEMA 3A is a marker for disease activity of systemic lupus erythematosus^[7].

Structural insights

SEMA interacts with plexin C1 via 3 regions: , and ^[8]. Water molecules are shown as red spheres.

3D structures of semaphorin

Semaphorin 3D structures

Glycosylated human semaphorin 7A (deeppink) complex with plexin-C1 (cyan) and Ca+2 ion (green), 3nvn

Drag the structure with the mouse to rotate

ReferencesReferences

↑ Nakamura F, Kalb RG, Strittmatter SM. Molecular basis of semaphorin-mediated axon guidance. J Neurobiol. 2000 Aug;44(2):219-29. PMID:10934324
↑ Behar O, Golden JA, Mashimo H, Schoen FJ, Fishman MC. Semaphorin III is needed for normal patterning and growth of nerves, bones and heart. Nature. 1996 Oct 10;383(6600):525-8. PMID:8849723 doi:http://dx.doi.org/10.1038/383525a0
↑ Yang YH, Buhamrah A, Schneider A, Lin YL, Zhou H, Bugshan A, Basile JR. Semaphorin 4D Promotes Skeletal Metastasis in Breast Cancer. PLoS One. 2016 Feb 24;11(2):e0150151. doi: 10.1371/journal.pone.0150151., eCollection 2016. PMID:26910109 doi:http://dx.doi.org/10.1371/journal.pone.0150151
↑ Kang S, Nakanishi Y, Kioi Y, Okuzaki D, Kimura T, Takamatsu H, Koyama S, Nojima S, Nishide M, Hayama Y, Kinehara Y, Kato Y, Nakatani T, Shimogori T, Takagi J, Toyofuku T, Kumanogoh A. Semaphorin 6D reverse signaling controls macrophage lipid metabolism and anti-inflammatory polarization. Nat Immunol. 2018 Jun;19(6):561-570. PMID:29777213 doi:10.1038/s41590-018-0108-0
↑ Pasterkamp RJ, Peschon JJ, Spriggs MK, Kolodkin AL. Semaphorin 7A promotes axon outgrowth through integrins and MAPKs. Nature. 2003 Jul 24;424(6947):398-405. PMID:12879062 doi:http://dx.doi.org/10.1038/nature01790
↑ Pasterkamp RJ, Giger RJ. Semaphorin function in neural plasticity and disease. Curr Opin Neurobiol. 2009 Jun;19(3):263-74. doi: 10.1016/j.conb.2009.06.001. Epub, 2009 Jun 21. PMID:19541473 doi:http://dx.doi.org/10.1016/j.conb.2009.06.001
↑ Vadasz Z, Toubi E. Semaphorin 3A - a marker for disease activity and a potential putative disease-modifying treatment in systemic lupus erythematosus. Lupus. 2012 Oct;21(12):1266-70. Epub 2012 Aug 8. PMID:22875653 doi:http://dx.doi.org/10.1177/0961203312456753
↑ Liu H, Juo ZS, Shim AH, Focia PJ, Chen X, Garcia KC, He X. Structural basis of semaphorin-plexin recognition and viral mimicry from Sema7A and A39R complexes with PlexinC1. Cell. 2010 Sep 3;142(5):749-61. Epub 2010 Aug 19. PMID:20727575 doi:10.1016/j.cell.2010.07.040

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Michal Harel, Alexander Berchansky

[1] Nakamura F, Kalb RG, Strittmatter SM. Molecular basis of semaphorin-mediated axon guidance. J Neurobiol. 2000 Aug;44(2):219-29. PMID:10934324

[2] Behar O, Golden JA, Mashimo H, Schoen FJ, Fishman MC. Semaphorin III is needed for normal patterning and growth of nerves, bones and heart. Nature. 1996 Oct 10;383(6600):525-8. PMID:8849723 doi:http://dx.doi.org/10.1038/383525a0

[3] Yang YH, Buhamrah A, Schneider A, Lin YL, Zhou H, Bugshan A, Basile JR. Semaphorin 4D Promotes Skeletal Metastasis in Breast Cancer. PLoS One. 2016 Feb 24;11(2):e0150151. doi: 10.1371/journal.pone.0150151., eCollection 2016. PMID:26910109 doi:http://dx.doi.org/10.1371/journal.pone.0150151

[4] Kang S, Nakanishi Y, Kioi Y, Okuzaki D, Kimura T, Takamatsu H, Koyama S, Nojima S, Nishide M, Hayama Y, Kinehara Y, Kato Y, Nakatani T, Shimogori T, Takagi J, Toyofuku T, Kumanogoh A. Semaphorin 6D reverse signaling controls macrophage lipid metabolism and anti-inflammatory polarization. Nat Immunol. 2018 Jun;19(6):561-570. PMID:29777213 doi:10.1038/s41590-018-0108-0

[5] Pasterkamp RJ, Peschon JJ, Spriggs MK, Kolodkin AL. Semaphorin 7A promotes axon outgrowth through integrins and MAPKs. Nature. 2003 Jul 24;424(6947):398-405. PMID:12879062 doi:http://dx.doi.org/10.1038/nature01790

[6] Pasterkamp RJ, Giger RJ. Semaphorin function in neural plasticity and disease. Curr Opin Neurobiol. 2009 Jun;19(3):263-74. doi: 10.1016/j.conb.2009.06.001. Epub, 2009 Jun 21. PMID:19541473 doi:http://dx.doi.org/10.1016/j.conb.2009.06.001

[7] Vadasz Z, Toubi E. Semaphorin 3A - a marker for disease activity and a potential putative disease-modifying treatment in systemic lupus erythematosus. Lupus. 2012 Oct;21(12):1266-70. Epub 2012 Aug 8. PMID:22875653 doi:http://dx.doi.org/10.1177/0961203312456753

[8] Liu H, Juo ZS, Shim AH, Focia PJ, Chen X, Garcia KC, He X. Structural basis of semaphorin-plexin recognition and viral mimicry from Sema7A and A39R complexes with PlexinC1. Cell. 2010 Sep 3;142(5):749-61. Epub 2010 Aug 19. PMID:20727575 doi:10.1016/j.cell.2010.07.040

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