SEMA4D explained

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.^[1]

Function

Semaphorin 4D (Sema 4D) is an axon guidance molecule which is secreted by oligodendrocytes and induces growth cone collapse in the central nervous system. By binding plexin B1 receptor it functions as an R-Ras GTPase-activating protein (GAP) and repels axon growth cones in both the mature central nervous system.^[2]

In the immune system, CD100 binds CD72 to activate B cells and dendritic cells, though much about this interaction is still under investigation.^{[3] [4]}

During skin damage repairs, SEMA4D interacts with Plexin B2 on Gamma delta T cells to play a role in the healing process.^[5]

See also

• Cluster of differentiation

Further reading

• Bougeret C, Mansur IG, Dastot H, etal . Increased surface expression of a newly identified 150-kDa dimer early after human T lymphocyte activation . J. Immunol. . 148 . 2 . 318–23 . 1992 . 10.4049/jimmunol.148.2.318 . 1530858 . 29224711 . free .
• Hall KT, Boumsell L, Schultze JL, etal . Human CD100, a novel leukocyte semaphorin that promotes B-cell aggregation and differentiation . Proc. Natl. Acad. Sci. U.S.A. . 93 . 21 . 11780–5 . 1996 . 8876214 . 10.1073/pnas.93.21.11780 . 38135 . 1996PNAS...9311780H . free .
• Herold C, Elhabazi A, Bismuth G, etal . CD100 is associated with CD45 at the surface of human T lymphocytes. Role in T cell homotypic adhesion . J. Immunol. . 157 . 12 . 5262–8 . 1997 . 10.4049/jimmunol.157.12.5262 . 8955171 . 36341775 . free .
• Furuyama T, Inagaki S, Kosugi A, etal . Identification of a novel transmembrane semaphorin expressed on lymphocytes . J. Biol. Chem. . 271 . 52 . 33376–81 . 1997 . 8969198 . 10.1074/jbc.271.52.33376 . free .
• Tamagnone L, Artigiani S, Chen H, etal . Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates . Cell . 99 . 1 . 71–80 . 1999 . 10520995 . 10.1016/S0092-8674(00)80063-X . 17386412 . free .
• Elhabazi A, Delaire S, Bensussan A, etal . Biological activity of soluble CD100. I. The extracellular region of CD100 is released from the surface of T lymphocytes by regulated proteolysis . J. Immunol. . 166 . 7 . 4341–7 . 2001 . 11254687 . 10.4049/jimmunol.166.7.4341. free .
• Delaire S, Billard C, Tordjman R, etal . Biological activity of soluble CD100. II. Soluble CD100, similarly to H-SemaIII, inhibits immune cell migration . J. Immunol. . 166 . 7 . 4348–54 . 2001 . 11254688 . 10.4049/jimmunol.166.7.4348. free .
• Vikis HG, Li W, Guan KL . The Plexin-B1/Rac interaction inhibits PAK activation and enhances Sema4D ligand binding . Genes Dev. . 16 . 7 . 836–45 . 2002 . 11937491 . 10.1101/gad.966402 . 186329 .
• Granziero L, Circosta P, Scielzo C, etal . CD100/Plexin-B1 interactions sustain proliferation and survival of normal and leukemic CD5+ B lymphocytes . Blood . 101 . 5 . 1962–9 . 2003 . 12406905 . 10.1182/blood-2002-05-1339 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Izmailova E, Bertley FM, Huang Q, etal . HIV-1 Tat reprograms immature dendritic cells to express chemoattractants for activated T cells and macrophages . Nat. Med. . 9 . 2 . 191–7 . 2003 . 12539042 . 10.1038/nm822 . 26145639 .
• Love CA, Harlos K, Mavaddat N, etal . The ligand-binding face of the semaphorins revealed by the high-resolution crystal structure of SEMA4D . Nat. Struct. Biol. . 10 . 10 . 843–8 . 2003 . 12958590 . 10.1038/nsb977 . 24468463 .
• Giraudon P, Vincent P, Vuaillat C, etal . Semaphorin CD100 from activated T lymphocytes induces process extension collapse in oligodendrocytes and death of immature neural cells . J. Immunol. . 172 . 2 . 1246–55 . 2004 . 14707103 . 10.4049/jimmunol.172.2.1246. free .
• Gerhard DS, Wagner L, Feingold EA, etal . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Deaglio S, Vaisitti T, Bergui L, etal . CD38 and CD100 lead a network of surface receptors relaying positive signals for B-CLL growth and survival . Blood . 105 . 8 . 3042–50 . 2005 . 15613544 . 10.1182/blood-2004-10-3873 . free .
• Conrotto P, Valdembri D, Corso S, etal . Sema4D induces angiogenesis through Met recruitment by Plexin B1 . Blood . 105 . 11 . 4321–9 . 2005 . 15632204 . 10.1182/blood-2004-07-2885 . free .
• Basile JR, Afkhami T, Gutkind JS . Semaphorin 4D/Plexin-B1 Induces Endothelial Cell Migration through the Activation of PYK2, Src, and the Phosphatidylinositol 3-Kinase-Akt Pathway . Mol. Cell. Biol. . 25 . 16 . 6889–98 . 2005 . 16055703 . 10.1128/MCB.25.16.6889-6898.2005 . 1190270 .
• Lewandrowski U, Moebius J, Walter U, Sickmann A . Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach . Mol. Cell. Proteomics . 5 . 2 . 226–33 . 2006 . 16263699 . 10.1074/mcp.M500324-MCP200 . free .
• Nkyimbeng-Takwi EH, Chapoval SP . Biology and function of neuroimmune semaphorins 4A and 4D . Immunol. Res.. 50 . 1 . 10–21. 2011 . 21203905 . 3366695 . 10.1007/s12026-010-8201-y.
• Smith EP, Shanks K, Lipsky MM, DeTolla LJ, Keegan AD, Chapoval SP . Expression of neuroimmune semaphorins 4A and 4D and their receptors in the lung is enhanced by allergen and vascular endothelial growth factor . BMC Immunol. . 12. 30. 2011. 21595947 . 3118960 . 10.1186/1471-2172-12-30 . free .
• Shanks K, Nkyimbeng-Takwi EH, Smith EP, Lipsky MM, DeTolla LJ, Keegan AD, Chapoval SP . Neuroimmune semaphorin 4D is necessary for optimal lung allergic inflammation . Mol. Immunol. . 56 . 4 . 480–7. 2013. 23911404 . 10.1016/j.molimm.2013.05.228 . 3783523.

Notes and References

1. Web site: Entrez Gene: SEMA4D sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4D.
2. Ito Y, Oinuma I, Katoh H, Kaibuchi K, Negishi M . Sema4D/plexin-B1 activates GSK-3β through R-Ras GAP activity, inducing growth cone collapse . EMBO Reports . 7 . 7 . 704–9 . July 2006 . 16799460 . 1500830 . 10.1038/sj.embor.7400737 .
3. Kumanogoh A, Watanabe C, Lee I, Wang X, Shi W, Araki H, Hirata H, Iwahori K, Uchida J, Yasui T, Matsumoto M, Yoshida K, Yakura H, Pan C, Parnes JR, Kikutani H . Identification of CD72 as a lymphocyte receptor for the class IV semaphorin CD100: a novel mechanism for regulating B cell signaling . Immunity . 13 . 5 . 621–31 . November 2000 . 11114375 . 10.1016/S1074-7613(00)00062-5. free .
4. Ishida I, Kumanogoh A, Suzuki K, Akahani S, Noda K, Kikutani H . Involvement of CD100, a lymphocyte semaphorin, in the activation of the human immune system via CD72: implications for the regulation of immune and inflammatory responses . Int. Immunol. . 15 . 8 . 1027–34 . August 2003 . 12882840 . 10.1093/intimm/dxg098. free .
5. Deborah A. Witherden . Megumi Watanabe . Olivia Garijo . Stephanie E. Rieder . Gor Sarkisyan. Shane J.F. Cronin . Petra Verdino. Ian A. Wilson . Atsushi Kumanogoh . Hitoshi Kikutani . Luc Teyton . Wolfgang H. Fischer . Wendy L. Havran . The CD100 Receptor Interacts with Its Plexin B2 Ligand to Regulate Epidermal γδ T Cell Function . Immunity . 37 . 2 . 314–25 . August 2012 . 10.1016/j.immuni.2012.05.026. 22902232 . 3430606 .