Semaphorin

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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 7A promotes axon growth through integrins and MAPKs [4].

Relevance

SEMAs ar implicated in a number of developmental, psychiatric and neurodegenerative disorders[5]. SEMA 3A is a marker for disease activity of systemic lupus erythematosus[6].

Structural insights

SEMA interacts with plexin C1 via 3 regions: , and [7]. Water molecules are shown as red spheres.

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

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3D structures of semaphorin3D structures of semaphorin

Semaphorin 3D structures

15-March-2022

ReferencesReferences

  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. ↑ 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
  5. ↑ 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
  6. ↑ 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
  7. ↑ 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
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