Immune plexins and semaphorins: old proteins, new immune functions

Abstract

Plexins and semaphorins are a large family of proteins that are involved in cell movement and response. The importance of plexins and semaphorins has been emphasized by their discovery in many organ systems including the nervous (Nkyimbeng-Takwi and Chapoval, 2011; McCormick and Leipzig, 2012; Yaron and Sprinzak, 2012), epithelial (Miao et al., 1999; Fujii et al., 2002), and immune systems (Takamatsu and Kumanogoh, 2012) as well as diverse cell processes including angiogenesis (Serini et al., 2009; Sakurai et al., 2012), embryogenesis (Perala et al., 2012), and cancer (Potiron et al., 2009; Micucci et al., 2010). Plexins and semaphorins are transmembrane proteins that share a conserved extracellular semaphorin domain (Hota and Buck, 2012). The plexins and semaphorins are divided into four and eight subfamilies respectively based on their structural homology. Semaphorins are relatively small proteins containing the extracellular semaphorin domain and short intracellular tails. Plexins contain the semaphorin domain and long intracellular tails (Hota and Buck, 2012). The majority of plexin and semaphorin research has focused on the nervous system, particularly the developing nervous system, where these proteins are found to mediate many common neuronal cell processes including cell movement, cytoskeletal rearrangement, and signal transduction (Choi et al., 2008; Takamatsu et al., 2010). Their roles in the immune system are the focus of this review.

Keywords

plexin / semaphorin / immune system / dendritic cell / B cell / T cell

References

[1] (1999). Unified nomenclature for the semaphorins/collapsins. Semaphorin Nomenclature Committee. Cell 97, 551-552 .
[2] Adachi, T., Flaswinkel, H., Yakura, H., Reth, M., and Tsubata, T. (1998). The B cell surface protein CD72 recruits the tyrosine phosphatase SHP-1 upon tyrosine phosphorylation. J Immunol 160, 4662-4665 .
[3] Antipenko, A., Himanen, J.P., van Leyen, K., Nardi-Dei, V., Lesniak, J., Barton, W.A., Rajashankar, K.R., Lu, M., Hoemme, C., Puschel, A.W., . (2003). Structure of the semaphorin-3A receptor binding module. Neuron 39, 589-598 .10.1016/S0896-6273(03)00502-6
[4] Aravind, L., and Koonin, E.V. (1999). Gleaning non-trivial structural, functional and evolutionary information about proteins by iterative database searches. J Mol Biol 287, 1023-1040 10.1006/jmbi.1999.2653
[5] Artigiani, S., Barberis, D., Fazzari, P., Longati, P., Angelini, P., van de Loo, J.W., Comoglio, P.M., and Tamagnone, L. (2003). Functional regulation of semaphorin receptors by proprotein convertases. J Biol Chem 278, 10094-10101 .10.1074/jbc.M210156200
[6] Artigiani, S., Comoglio, P.M., and Tamagnone, L. (1999). Plexins, semaphorins, and scatter factor receptors: a common root for cell guidance signals? IUBMB Life 48, 477-482 .
[7] Asselin-Paturel, C., Brizard, G., Chemin, K., Boonstra, A., O'Garra, A., Vicari, A., and Trinchieri, G. (2005). Type I interferon dependence of plasmacytoid dendritic cell activation and migration. The Journal of experimental medicine 201, 1157-1167 .10.1084/jem.20041930
[8] Baker, J.R., Jr. (2009). Dendrimer-based nanoparticles for cancer therapy. Hematology Am Soc Hematol Educ Program , 708-719 .10.1182/asheducation-2009.1.708
[9] Bark, H., Xu, H.D., Kim, S.H., Yun, J., and Choi, C.H. (2008). P-glycoprotein down-regulates expression of breast cancer resistance protein in a drug-free state. FEBS Lett 582, 2595-2600 .10.1016/j.febslet.2008.06.036
[10] Basilico, C., Arnesano, A., Galluzzo, M., Comoglio, P.M., and Michieli, P. (2008). A high affinity hepatocyte growth factor-binding site in the immunoglobulin-like region of Met. J Biol Chem 283, 21267-21277. 10.1074/jbc.M800727200
[11] Bork, P., Doerks, T., Springer, T.A., and Snel, B. (1999). Domains in plexins: links to integrins and transcription factors. Trends Biochem Sci 24, 261-263 .10.1016/S0968-0004(99)01416-4
[12] Chabbert-de Ponnat, I., Marie-Cardine, A., Pasterkamp, R.J., Schiavon, V., Tamagnone, L., Thomasset, N., Bensussan, A., and Boumsell, L. (2005). Soluble CD100 functions on human monocytes and immature dendritic cells require plexin C1 and plexin B1, respectively. Int Immunol 17, 439-447 .10.1093/intimm/dxh224
[13] Chakravarti, S., Sabatos, C.A., Xiao, S., Illes, Z., Cha, E.K., Sobel, R.A., Zheng, X.X., Strom, T.B., and Kuchroo, V.K. (2005). Tim-2 regulates T helper type 2 responses and autoimmunity. J Exp Med 202, 437-444 .10.1084/jem.20050308
[14] Chauvet, S., Cohen, S., Yoshida, Y., Fekrane, L., Livet, J., Gayet, O., Segu, L., Buhot, M.C., Jessell, T.M., Henderson, C.E., . (2007). Gating of Sema3E/PlexinD1 signaling by neuropilin-1 switches axonal repulsion to attraction during brain development. Neuron 56, 807-822 .10.1016/j.neuron.2007.10.019
[15] Chen, Z., Koralov, S.B., Gendelman, M., Carroll, M.C., and Kelsoe, G. (2000). Humoral immune responses in Cr2-/- mice: enhanced affinity maturation but impaired antibody persistence. J Immunol 164, 4522-4532 .
[16] Choi, Y.I., Duke-Cohan, J.S., Ahmed, W.B., Handley, M.A., Mann, F., Epstein, J.A., Clayton, L.K., and Reinherz, E.L. (2008). PlexinD1 glycoprotein controls migration of positively selected thymocytes into the medulla. Immunity 29, 888-898 .10.1016/j.immuni.2008.10.008
[17] Comeau, M.R., Johnson, R., DuBose, R.F., Petersen, M., Gearing, P., VandenBos, T., Park, L., Farrah, T., Buller, R.M., Cohen, J.I., . (1998). A poxvirus-encoded semaphorin induces cytokine production from monocytes and binds to a novel cellular semaphorin receptor, VESPR. Immunity 8, 473-482 .10.1016/S1074-7613(00)80552-X
[18] Delaire, S., Elhabazi, A., Bensussan, A., and Boumsell, L. (1998). CD100 is a leukocyte semaphorin. Cell Mol Life Sci 54, 1265-1276 .10.1007/s000180050252
[19] Elhabazi, A., Lang, V., Herold, C., Freeman, G.J., Bensussan, A., Boumsell, L., and Bismuth, G. (1997). The human semaphorin-like leukocyte cell surface molecule CD100 associates with a serine kinase activity. J Biol Chem 272, 23515-23520. 10.1074/jbc.272.38.23515
[20] Eun, S.Y., O'Connor, B.P., Wong, A.W., van Deventer, H.W., Taxman, D.J., Reed, W., Li, P., Blum, J.S., McKinnon, K.P., and Ting, J.P. (2006). Cutting edge: rho activation and actin polarization are dependent on plexin-A1 in dendritic cells. J Immunol 177, 4271-4275 .
[21] Fujii, T., Nakao, F., Shibata, Y., Shioi, G., Kodama, E., Fujisawa, H., and Takagi, S. (2002). Caenorhabditis elegans PlexinA, PLX-1, interacts with transmembrane semaphorins and regulates epidermal morphogenesis. Development 129, 2053-2063 .
[22] Fujisawa, H. (2004). Discovery of semaphorin receptors, neuropilin and plexin, and their functions in neural development. J Neurobiol 59, 24-33 .10.1002/neu.10337
[23] Fujisawa, H., Ohtsuki, T., Takagi, S., and Tsuji, T. (1989). An aberrant retinal pathway and visual centers in Xenopus tadpoles share a common cell surface molecule, A5 antigen. Dev Biol 135, 231-240 .10.1016/0012-1606(89)90175-9
[24] Gherardi, E., Love, C.A., Esnouf, R.M., and Jones, E.Y. (2004). The sema domain. Curr Opin Struct Biol 14, 669-678 .10.1016/j.sbi.2004.10.010
[25] Gitler, A.D., Lu, M.M., and Epstein, J.A. (2004). PlexinD1 and semaphorin signaling are required in endothelial cells for cardiovascular development. Dev Cell 7, 107-116 .10.1016/j.devcel.2004.06.002
[26] Granziero, L., Circosta, P., Scielzo, C., Frisaldi, E., Stella, S., Geuna, M., Giordano, S., Ghia, P., and Caligaris-Cappio, F. (2003). CD100/Plexin-B1 interactions sustain proliferation and survival of normal and leukemic CD5+ B lymphocytes. Blood 101, 1962-1969 .10.1182/blood-2002-05-1339
[27] Gu, C., Yoshida, Y., Livet, J., Reimert, D.V., Mann, F., Merte, J., Henderson, C.E., Jessell, T.M., Kolodkin, A.L., and Ginty, D.D. (2005). Semaphorin 3E and plexin-D1 control vascular pattern independently of neuropilins. Science 307, 265-268 .10.1126/science.1105416
[28] Hall, K.T., Boumsell, L., Schultze, J.L., Boussiotis, V.A., Dorfman, D.M., Cardoso, A.A., Bensussan, A., Nadler, L.M., and Freeman, G.J. (1996). Human CD100, a novel leukocyte semaphorin that promotes B-cell aggregation and differentiation. Proc Natl Acad Sci U S A 93, 11780-11785 .10.1073/pnas.93.21.11780
[29] Harris, W.A., Holt, C.E., and Bonhoeffer, F. (1987). Retinal axons with and without their somata, growing to and arborizing in the tectum of Xenopus embryos: a time-lapse video study of single fibres in vivo. Development 101, 123-133 .
[30] Holl, E.K., O'Connor, B.P., Holl, T.M., Roney, K.E., Zimmermann, A.G., Jha, S., Kelsoe, G., and Ting, J.P. (2011). Plexin-D1 is a novel regulator of germinal centers and humoral immune responses. J Immunol 186, 5603-5611 .10.4049/jimmunol.1003464
[31] Hota, P.K., and Buck, M. (2012). Plexin structures are coming: opportunities for multilevel investigations of semaphorin guidance receptors, their cell signaling mechanisms, and functions. Cell Mol Life Sci 69, 2765-3805 .10.1007/s00018-012-1019-0
[32] Huang, C., Lu, C., and Springer, T.A. (1997). Folding of the conserved domain but not of flanking regions in the integrin beta2 subunit requires association with the alpha subunit. Proc Natl Acad Sci U S A 94, 3156-3161 .10.1073/pnas.94.7.3156
[33] Huber, A.B., Kolodkin, A.L., Ginty, D.D., and Cloutier, J.F. (2003). Signaling at the growth cone: ligand-receptor complexes and the control of axon growth and guidance. Annu Rev Neurosci 26, 509-563 .10.1146/annurev.neuro.26.010302.081139
[34] Hur, E.H., Lee, J.H., Lee, M.J., Choi, S.J., Kang, M.J., Seol, M., Jang, Y.E., Lee, H.J., Kang, I.S., Shim, S.K., . (2008). C3435T polymorphism of the MDR1 gene is not associated with P-glycoprotein function of leukemic blasts and clinical outcome in patients with acute myeloid leukemia. Leuk Res 32, 1601-1604 .10.1016/j.leukres.2007.12.013
[35] Ishida, I., Kumanogoh, A., Suzuki, K., Akahani, S., Noda, K., and Kikutani, H. (2003). 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, 1027-1034 .10.1093/intimm/dxg098
[36] Janssen, B.J., Robinson, R.A., Perez-Branguli, F., Bell, C.H., Mitchell, K.J., Siebold, C., and Jones, E.Y. (2010). Structural basis of semaphorin-plexin signalling. Nature 467, 1118-1122.10.1038/nature09468
[37] Ji, J.D., Park-Min, K.H., and Ivashkiv, L.B. (2009). Expression and function of semaphorin 3A and its receptors in human monocyte-derived macrophages. Human Immunol 70, 211-217 .10.1016/j.humimm.2009.01.026
[38] Klostermann, A., Lohrum, M., Adams, R.H., and Puschel, A.W. (1998). The chemorepulsive activity of the axonal guidance signal semaphorin D requires dimerization. J Biol Chem 273, 7326-7331 .10.1074/jbc.273.13.7326
[39] Kruger, R.P., Aurandt, J., and Guan, K.L. (2005). Semaphorins command cells to move. Nat Rev Mol Cell Biol 6, 789-800 .10.1038/nrm1740
[40] Kuchroo, V.K., Umetsu, D.T., DeKruyff, R.H., and Freeman, G.J. (2003). The TIM gene family: emerging roles in immunity and disease. Nature reviews. Immunology 3, 454-462 .10.1038/nri1111
[41] Kumanogoh, A., Marukawa, S., Suzuki, K., Takegahara, N., Watanabe, C., Ch'ng, E., Ishida, I., Fujimura, H., Sakoda, S., Yoshida, K., . (2002). Class IV semaphorin Sema4A enhances T-cell activation and interacts with Tim-2. Nature 419, 629-633 .10.1038/nature01037
[42] Kumanogoh, A., Shikina, T., Suzuki, K., Uematsu, S., Yukawa, K., Kashiwamura, S., Tsutsui, H., Yamamoto, M., Takamatsu, H., Ko-Mitamura, E.P., . (2005). Nonredundant roles of Sema4A in the immune system: defective T cell priming and Th1/Th2 regulation in Sema4A-deficient mice. Immunity 22, 305-316 .10.1016/j.immuni.2005.01.014
[43] Kumanogoh, A., Watanabe, C., Lee, I., Wang, X., Shi, W., Araki, H., Hirata, H., Iwahori, K., Uchida, J., Yasui, T., . (2000). Identification of CD72 as a lymphocyte receptor for the class IV semaphorin CD100: a novel mechanism for regulating B cell signaling. Immunity 13, 621-631 .10.1016/S1074-7613(00)00062-5
[44] Liu, H., Juo, Z.S., Shim, A.H., Focia, P.J., Chen, X., Garcia, K.C., and He, X. (2010). Structural basis of semaphorin-plexin recognition and viral mimicry from Sema7A and A39R complexes with PlexinC1. Cell 142, 749-761 .10.1016/j.cell.2010.07.040
[45] Luo, Y., Raible, D., and Raper, J.A. (1993). Collapsin: a protein in brain that induces the collapse and paralysis of neuronal growth cones. Cell 75, 217-227 .10.1016/0092-8674(93)80064-L
[46] Luo, Y., Shepherd, I., Li, J., Renzi, M.J., Chang, S., and Raper, J.A. (1995). A family of molecules related to collapsin in the embryonic chick nervous system. Neuron 14, 1131-1140 .10.1016/0896-6273(95)90261-9
[47] Maestrini, E., Tamagnone, L., Longati, P., Cremona, O., Gulisano, M., Bione, S., Tamanini, F., Neel, B.G., Toniolo, D., and Comoglio, P.M. (1996). A family of transmembrane proteins with homology to the MET-hepatocyte growth factor receptor. Proc Natl Acad Sci U S A 93, 674-678 .10.1073/pnas.93.2.674
[48] Makino, N., Toyofuku, T., Takegahara, N., Takamatsu, H., Okuno, T., Nakagawa, Y., Kang, S., Nojima, S., Hori, M., Kikutani, H., . (2008). Involvement of Sema4A in the progression of experimental autoimmune myocarditis. FEBS Lett 582, 3935-3940 .10.1016/j.febslet.2008.10.040
[49] McCormick, A.M., and Leipzig, N.D. (2012). Neural regenerative strategies incorporating biomolecular axon guidance signals. Ann Biomed Eng 40, 578-597 .10.1007/s10439-011-0505-0
[50] Meda, C., Molla, F., De Pizzol, M., Regano, D., Maione, F., Capano, S., Locati, M., Mantovani, A., Latini, R., Bussolino, F., . (2012). Semaphorin 4A exerts a proangiogenic effect by enhancing vascular endothelial growth factor-A expression in macrophages. J Immunol 188, 4081-4092 .10.4049/jimmunol.1101435
[51] Miao, H.Q., Soker, S., Feiner, L., Alonso, J.L., Raper, J.A., and Klagsbrun, M. (1999). Neuropilin-1 mediates collapsin-1/semaphorin III inhibition of endothelial cell motility: functional competition of collapsin-1 and vascular endothelial growth factor-165. J Cell Biol 146, 233-242 .
[52] Micucci, C., Orciari, S., and Catalano, A. (2010). Semaphorins and their receptors in stem and cancer cells. Curr Med Chem 17, 3462-3475 .10.2174/092986710792927796
[53] Mizui, M., Kumanogoh, A., and Kikutani, H. (2009). Immune semaphorins: novel features of neural guidance molecules. J Clin Immunol 29, 1-11. 10.1007/s10875-008-9263-7
[54] Muratori, C., and Tamagnone, L. (2012). Semaphorin signals tweaking the tumor microenvironment. Adv Cancer Res 114, 59-85 .
[55] Nkyimbeng-Takwi, E., and Chapoval, S.P. (2011). Biology and function of neuroimmune semaphorins 4A and 4D. Immunol Res 50, 10-21 .10.1007/s12026-010-8201-y
[56] Nogi, T., Yasui, N., Mihara, E., Matsunaga, Y., Noda, M., Yamashita, N., Toyofuku, T., Uchiyama, S., Goshima, Y., Kumanogoh, A., . (2010). Structural basis for semaphorin signalling through the plexin receptor. Nature 467, 1123-1127 .10.1038/nature09473
[57] O'Connor, B.P., Eun, S.Y., Ye, Z., Zozulya, A.L., Lich, J.D., Moore, C.B., Iocca, H.A., Roney, K.E., Holl, E.K., Wu, Q.P., . (2008). Semaphorin 6D regulates the late phase of CD4+ T cell primary immune responses. Proc Natl Acad Sci U S A 105, 13015-13020 .10.1073/pnas.0803386105
[58] Ohta, K., Mizutani, A., Kawakami, A., Murakami, Y., Kasuya, Y., Takagi, S., Tanaka, H., and Fujisawa, H. (1995). Plexin: a novel neuronal cell surface molecule that mediates cell adhesion via a homophilic binding mechanism in the presence of calcium ions. Neuron 14, 1189-1199 .10.1016/0896-6273(95)90266-X
[59] Ohta, K., Takagi, S., Asou, H., and Fujisawa, H. (1992). Involvement of neuronal cell surface molecule B2 in the formation of retinal plexiform layers. Neuron 9, 151-161 .10.1016/0896-6273(92)90230-B
[60] Oinuma, I., Ishikawa, Y., Katoh, H., and Negishi, M. (2004). The Semaphorin 4D receptor Plexin-B1 is a GTPase activating protein for R-Ras. Science 305, 862-865 .10.1126/science.1097545
[61] Okuno, T., Nakatsuji, Y., Moriya, M., Takamatsu, H., Nojima, S., Takegahara, N., Toyofuku, T., Nakagawa, Y., Kang, S., Friedel, R.H., . (2010). Roles of Sema4D-plexin-B1 interactions in the central nervous system for pathogenesis of experimental autoimmune encephalomyelitis. J Immunol 184, 1499-1506 .10.4049/jimmunol.0903302
[62] Pasterkamp, R.J., and Kolodkin, A.L. (2003). Semaphorin junction: making tracks toward neural connectivity. Curr Opin Neurobiol 13, 79-89 .10.1016/S0959-4388(03)00003-5
[63] Perala, N., Sariola, H., and Immonen, T. (2012). More than nervous: the emerging roles of plexins. Differentiation 83, 77-91 .10.1016/j.diff.2011.08.001
[64] Potiron, V.A., Roche, J., and Drabkin, H.A. (2009). Semaphorins and their receptors in lung cancer. Cancer Lett 273, 1-14 .10.1016/j.canlet.2008.05.032
[65] Rizzolio, S., and Tamagnone, L. (2011). Multifaceted role of neuropilins in cancer. Curr Med Chem 18, 3563-3575 .10.2174/092986711796642544
[66] Rohm, B., Ottemeyer, A., Lohrum, M., and Puschel, A.W. (2000). Plexin/neuropilin complexes mediate repulsion by the axonal guidance signal semaphorin 3A. Mech Dev 93, 95-104 .10.1016/S0925-4773(00)00269-0
[67] Roney, K.E., O'Connor, B.P., Wen, H., Holl, E.K., Guthrie, E.H., Davis, B.K., Jones, S.W., Jha, S., Sharek, L., Garcia-Mata, R., . (2011). Plexin-B2 negatively regulates macrophage motility, Rac, and Cdc42 activation. PLoS ONE 6, e24795.10.1371/journal.pone.0024795
[68] Sakurai, A., Doci, C.L., and Gutkind, J.S. (2012). Semaphorin signaling in angiogenesis, lymphangiogenesis and cancer. Cell Res 22, 23-32 .10.1038/cr.2011.198
[69] Satoda, M., Takagi, S., Ohta, K., Hirata, T., and Fujisawa, H. (1995). Differential expression of two cell surface proteins, neuropilin and plexin, in Xenopus olfactory axon subclasses. J Neurosci 15, 942-955 .
[70] Serini, G., Maione, F., Giraudo, E., and Bussolino, F. (2009). Semaphorins and tumor angiogenesis. Angiogenesis 12, 187-193 .10.1007/s10456-009-9138-4
[71] Shi, W., Kumanogoh, A., Watanabe, C., Uchida, J., Wang, X., Yasui, T., Yukawa, K., Ikawa, M., Okabe, M., Parnes, J.R., . (2000). The class IV semaphorin CD100 plays nonredundant roles in the immune system: defective B and T cell activation in CD100-deficient mice. Immunity 13, 633-642 .10.1016/S1074-7613(00)00063-7
[72] Smith, E.P., Shanks, K., Lipsky, M.M., DeTolla, L.J., Keegan, A.D., and Chapoval, S.P. (2011). 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, 30.10.1186/1471-2172-12-30
[73] Sperry, R.W. (1963). Chemoaffinity in the orderly growth of nerve fiber patterns and connections, Vol 50.
[74] Suto, F., Tsuboi, M., Kamiya, H., Mizuno, H., Kiyama, Y., Komai, S., Shimizu, M., Sanbo, M., Yagi, T., Hiromi, Y., . (2007). Interactions between plexin-A2, plexin-A4, and semaphorin 6A control lamina-restricted projection of hippocampal mossy fibers. Neuron 53, 535-547 .10.1016/j.neuron.2007.01.028
[75] Suzuki, K., Okuno, T., Yamamoto, M., Pasterkamp, R.J., Takegahara, N., Takamatsu, H., Kitao, T., Takagi, J., Rennert, P.D., Kolodkin, A.L., . (2007). Semaphorin 7A initiates T-cell-mediated inflammatory responses through alpha1beta1 integrin. Nature 446, 680-684 .10.1038/nature05652
[76] Takagi, S., Hirata, T., Agata, K., Mochii, M., Eguchi, G., and Fujisawa, H. (1991). The A5 antigen, a candidate for the neuronal recognition molecule, has homologies to complement components and coagulation factors. Neuron 7, 295-307 .10.1016/0896-6273(91)90268-5
[77] Takagi, S., Tsuji, T., Amagai, T., Takamatsu, T., and Fujisawa, H. (1987). Specific cell surface labels in the visual centers of Xenopus laevis tadpole identified using monoclonal antibodies. Dev Biol 122, 90-100 .10.1016/0012-1606(87)90335-6
[78] Takahashi, T., Fournier, A., Nakamura, F., Wang, L.H., Murakami, Y., Kalb, R.G., Fujisawa, H., and Strittmatter, S.M. (1999). Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors. Cell 99, 59-69 .10.1016/S0092-8674(00)80062-8
[79] Takahashi, T., and Strittmatter, S.M. (2001). Plexina1 autoinhibition by the plexin sema domain. Neuron 29, 429-439 .10.1016/S0896-6273(01)00216-1
[80] Takamatsu, H., and Kumanogoh, A. (2012). Diverse roles for semaphorin-plexin signaling in the immune system. Trends Immunol 33, 127-135 .10.1016/j.it.2012.01.008
[81] Takamatsu, H., Takegahara, N., Nakagawa, Y., Tomura, M., Taniguchi, M., Friedel, R.H., Rayburn, H., Tessier-Lavigne, M., Yoshida, Y., Okuno, T., . (2010). Semaphorins guide the entry of dendritic cells into the lymphatics by activating myosin II. Nat Immunol 11, 594-600 .10.1038/ni.1885
[82] Takegahara, N., Takamatsu, H., Toyofuku, T., Tsujimura, T., Okuno, T., Yukawa, K., Mizui, M., Yamamoto, M., Prasad, D.V., Suzuki, K., . (2006). Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis. Nat Cell Biol 8, 615-622 .10.1038/ncb1416
[83] Tamagnone, L., Artigiani, S., Chen, H., He, Z., Ming, G.I., Song, H., Chedotal, A., Winberg, M.L., Goodman, C.S., Poo, M., . (1999). Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates. Cell 99, 71-80 .10.1016/S0092-8674(00)80063-X
[84] Tamura, M., Takeyama, Y., Yamamoto, M., Shima, K., Suzuki, K., Nakamura, T., Asano, T., and Yoshida, K. (2008). [A case of pulmonary inflammatory pseudotumor accompanied with increased serum immunoglobulin G levels and autoimmune pancreatitis]. Nihon Kokyuki Gakkai Zasshi 46, 909-914 .
[85] Torres-Vazquez, J., Gitler, A.D., Fraser, S.D., Berk, J.D., Van, N.P., Fishman, M.C., Childs, S., Epstein, J.A., and Weinstein, B.M. (2004). Semaphorin-plexin signaling guides patterning of the developing vasculature. Dev Cell 7, 117-123 .10.1016/j.devcel.2004.06.008
[86] Toyofuku, T., Yabuki, M., Kamei, J., Kamei, M., Makino, N., Kumanogoh, A., and Hori, M. (2007). Semaphorin-4A, an activator for T-cell-mediated immunity, suppresses angiogenesis via Plexin-D1. Embo J 26, 1373-1384 .10.1038/sj.emboj.7601589
[87] Watarai, H., Sekine, E., Inoue, S., Nakagawa, R., Kaisho, T., and Taniguchi, M. (2008). PDC-TREM, a plasmacytoid dendritic cell-specific receptor, is responsible for augmented production of type I interferon. Proc Natl Acad Sci U S A 105, 2993-2998 .10.1073/pnas.0710351105
[88] Wen, H., Lei, Y., Eun, S.Y., and Ting, J.P. (2010). Plexin-A4- semaphorin 3A signaling is required for Toll-like receptor- and sepsis-induced cytokine storm. J Exp Med 207, 2943-2957 .10.1084/jem.20101138
[89] Winberg, M.L., Noordermeer, J.N., Tamagnone, L., Comoglio, P.M., Spriggs, M.K., Tessier-Lavigne, M., and Goodman, C.S. (1998). Plexin A is a neuronal semaphorin receptor that controls axon guidance. Cell 95, 903-916 .10.1016/S0092-8674(00)81715-8
[90] Witherden, D.A., Watanabe, M., Garijo, O., Rieder, S.E., Sarkisyan, G., Cronin, S.J., Verdino, P., Wilson, I.A., Kumanogoh, A., Kikutani, H., . (2012). The CD100 Receptor Interacts with Its Plexin B2 Ligand to Regulate Epidermal gammadelta T Cell Function. Immunity 37, 314-325 .10.1016/j.immuni.2012.05.026
[91] Wong, A.W., Brickey, W.J., Taxman, D.J., van Deventer, H.W., Reed, W., Gao, J.X., Zheng, P., Liu, Y., Li, P., Blum, J.S., . (2003). CIITA-regulated plexin-A1 affects T-cell-dendritic cell interactions. Nat Immunol 4, 891-898 .10.1038/ni960
[92] Yaron, A., and Sprinzak, D. (2012). The cis side of juxtacrine signaling: a new role in the development of the nervous system. Trends Neurosci 35, 230-239 .10.1016/j.tins.2011.12.003
[93] Yoshida, Y. (2012). Semaphorin signaling in vertebrate neural circuit assembly. Front Mol Neurosci 5, 71.10.3389/fnmol.2012.00071
[94] Yoshida, Y., Han, B., Mendelsohn, M., and Jessell, T.M. (2006). PlexinA1 signaling directs the segregation of proprioceptive sensory axons in the developing spinal cord. Neuron 52, 775-788 .10.1016/j.neuron.2006.10.032
[95] Yu, D., Cook, M.C., Shin, D.M., Silva, D.G., Marshall, J., Toellner, K.M., Havran, W.L., Caroni, P., Cooke, M.P., Morse, H.C., . (2008). Axon growth and guidance genes identify T-dependent germinal centre B cells. Immunol Cell Biol 86, 3-14 .10.1038/sj.icb.7100123
[96] Zhou, Y., Gunput, R.A., and Pasterkamp, R.J. (2008). Semaphorin signaling: progress made and promises ahead. Trends Biochem Sci 33, 161-170 .10.1016/j.tibs.2008.01.006