Alternative titles; symbols
HGNC Approved Gene Symbol: PLXNB1
Cytogenetic location: 3p21.31 Genomic coordinates (GRCh38): 3:48,403,854-48,430,310 (from NCBI)
Maestrini et al. (1996) identified a new gene of the hepatocyte growth factor (HGF) receptor family of transmembrane proteins while searching for previously unknown genes in Xq28. They called the novel gene SEX (300022). They also found 3 autosomal genes of similar sequence, 1 of which they designated SEP. The cDNA sequence (FB7) was isolated by serendipity from a human fetal brain cDNA library. The SEP gene was expressed at highest levels in fetal kidney. See also 601054 and 601055.
Tamagnone et al. (1999) reported that PLXNB1 is a receptor for the transmembrane semaphorin SEMA4D, also called CD100 (601866).
Swiercz et al. (2002) found that exposure of rat hippocampal neurons to Sema4d resulted in axonal growth cone collapse. Noting the involvement of Plxnb1 and Sema4d on growth cone morphology, both Swiercz et al. (2002) and Vikis et al. (2002) performed experiments that documented the relocalization of Plxnb1 to the plasma membrane, where it can interact with Sema4d, following the binding of small GTPases and the mobilization of several signaling molecules.
Giordano et al. (2002) presented evidence for cross-talk between PLXNB1 and MET (164860) during invasive growth in epithelial cells. Binding of SEMA4D to PLXNB1 stimulated tyrosine kinase activity of MET, resulting in tyrosine phosphorylation of both receptors. This effect was not found in cells lacking MET expression.
Oinuma et al. (2004) reported that the SEMA4D receptor plexin B1 directly stimulates the intrinsic GTPase activity of RRAS (165090), a member of the Ras superfamily of small GTP-binding proteins that has been implicated in promoting cell adhesion and neurite outgrowth. This activity required the interaction of plexin B1 with RND1 (609038), a small GTP-binding protein of the Rho family. Downregulation of RRAS activity by the plexin B1/RND1 complex was essential for the SEMA4D-induced growth cone collapse in hippocampal neurons. Oinuma et al. (2004) concluded that plexin B1 mediates SEMA4D-induced repulsive axon guidance signaling by acting as a GTPase-activating protein for RRAS.
By screening a panel of human/hamster somatic cell hybrids, Maestrini et al. (1996) determined that the SEP gene maps to 3pter-p14.
Wong et al. (2007) identified 13 different somatic mutations in the cytoplasmic domain of the PLXNB1 gene in prostate cancer (176807) tissue. Mutations were found in 8 (89%) of 9 prostate cancer bone metastases, in 7 (41%) of 17 lymph node metastases, and in 41 (46%) of 89 primary cancers. Forty percent of prostate cancers contained the same mutation, and the majority of the primary tumors showed overexpression of the plexin-B1 protein. In vitro functional expression studies of the 3 most common mutations showed that the mutant proteins resulted in increased cell motility, invasion, adhesion, and lamellipodia extension compared to wildtype. The mutations acted by hindering RAC1 (602048) and RRAS binding and GTP activity. Wong et al. (2007) concluded that PLXNB1 plays a role in tumor progression and metastasis.
Crystal Structure
Janssen et al. (2010) presented crystal structures of cognate complexes of the semaphorin-binding regions of plexins B1 and A2 (601054) with semaphorin ectodomains (human PLXNB1-SEMA4D (601866) and murine PlxnA2-Sema6A (605885)), plus unliganded structures of PlxnA2(1-4) and Sema6A(ecto). These structures, together with biophysical and cellular assays of wildtype and mutant proteins, revealed that semaphorin dimers independently bind 2 plexin molecules and that signaling is critically dependent on the avidity of the resulting bivalent 2:2 complex (monomeric semaphorin binds plexin but fails to trigger signaling). The data of Janssen et al. (2010) favored a cell-cell signaling mechanism involving semaphorin-stabilized plexin dimerization, possibly followed by clustering, which is consistent with previous functional data. Furthermore, the shared generic architecture of the complexes, formed through conserved contacts of the amino-terminal 7-bladed beta-propeller (sema) domains of both semaphorin and plexin, suggested that a common mode of interaction triggers all semaphorin-plexin-based signaling, while distinct insertions within or between blades of the sema domains determine binding specificity.
Tamagnone et al. (1999) proposed a novel nomenclature for the genes of the plexin family, which they grouped into the A, B, C, and D subfamilies; the PLXN5 gene was renamed plexin B1 by them.
Negishi-Koga et al. (2011) found that both Sema4d -/- and Plxnb1 -/- mice had increased bone density due to increased osteoblastic bone formation. Sema4d was expressed exclusively in wildtype osteoclasts, and Plxnb1 was expressed on wildtype osteoblasts. Sema4d/Plxnb1 signaling inhibited bone formation via the small GTPase RhoA (165390), and RhoA activation likely involved the Plxnb1 binding partners Arhgef11 (605708) and Arhgef12 (604763). Downstream, activation of RhoA in osteoblasts suppressed Igf1 (147440) signaling and cell motility. Negishi-Koga et al. (2011) concluded that signaling between Sema4d-expressing osteoclasts and Plxnb1-expressing osteoblasts regulates bone formation.
Giordano, S., Corso, S., Conrotto, P., Artigiani, S., Gilestro, G., Barberis, D., Tamagnone, L., Comoglio, P. M. The Semaphorin 4D receptor controls invasive growth by coupling with Met. Nature Cell Biol. 4: 720-724, 2002. [PubMed: 12198496] [Full Text: https://doi.org/10.1038/ncb843]
Janssen, B. J. C., Robinson, R. A., Perez-Branguli, F., Bell, C. H., Mitchell, K. J., Siebold, C., Jones, E. Y. Structural basis of semaphorin-plexin signalling. Nature 467: 1118-1122, 2010. [PubMed: 20877282] [Full Text: https://doi.org/10.1038/nature09468]
Maestrini, E., Tamagnone, L., Longati, P., Cremona, O., Gulisano, M., Bione, S., Tamanini, F., Neel, B. G., Toniolo, D., Comoglio, P. M. A family of transmembrane proteins with homology to the MET-hepatocyte growth factor receptor. Proc. Nat. Acad. Sci. 93: 674-678, 1996. [PubMed: 8570614] [Full Text: https://doi.org/10.1073/pnas.93.2.674]
Negishi-Koga, T., Shinohara, M., Komatsu, N., Bito, H., Kodama, T., Friedel, R. H., Takayanagi, H. Suppression of bone formation by osteoclastic expression of semaphorin 4D. Nature Med. 17: 1473-1480, 2011. [PubMed: 22019888] [Full Text: https://doi.org/10.1038/nm.2489]
Oinuma, I., Ishikawa, Y., Katoh, H., Negishi, M. The semaphorin 4D receptor plexin-B1 is a GTPase activating protein for R-Ras. Science 305: 862-865, 2004. [PubMed: 15297673] [Full Text: https://doi.org/10.1126/science.1097545]
Swiercz, J. M., Kuner, R., Behrens, J., Offermanns, S. Plexin-B1 directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth cone morphology. Neuron 35: 51-63, 2002. [PubMed: 12123608] [Full Text: https://doi.org/10.1016/s0896-6273(02)00750-x]
Tamagnone, L., Artigiani, S., Chen, H., He, Z., Ming, G., Song, H., Chedotal, A., Winberg, M. L., Goodman, C. S., Poo, M., Tessier-Lavigne, M., Comoglio, P. M. Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates. Cell 99: 71-80, 1999. Note: Erratum: Cell 104: following 320, 2001. [PubMed: 10520995] [Full Text: https://doi.org/10.1016/s0092-8674(00)80063-x]
Vikis, H. G., Li, W., Guan, K.-L. The plexin-B1/Rac interaction inhibits PAK activation and enhances Sema4D ligand binding. Genes Dev. 16: 836-845, 2002. [PubMed: 11937491] [Full Text: https://doi.org/10.1101/gad.966402]
Wong, O. G.-W., Nitkunan, T., Oinuma, I., Zhou, C., Blanc, V., Brown, R. S. D., Bott, S. R. J., Nariculam, J., Box, G., Munson, P., Constantinou, J., Feneley, M. R., Klocker, H., Eccles, S. A., Negishi, M., Freeman, A., Masters, J. R., Williamson, M. Plexin-B1 mutations in prostate cancer. Proc. Nat. Acad. Sci. 104: 19040-19045, 2007. [PubMed: 18024597] [Full Text: https://doi.org/10.1073/pnas.0702544104]