Ephrin B3 Explained

Ephrin-B3 is a protein that in humans is encoded by the EFNB3 gene.^{[1] [2]}

EFNB3, a member of the ephrin gene family, is important in brain development as well as in its maintenance. The EPH and EPH-related receptors comprise the largest subfamily of receptor protein-tyrosine kinases. EPH receptors typically have a single kinase domain and an extracellular region containing a Cysteine-rich domain and 2 fibronectin type III repeats. The ephrin ligands and receptors have been named by the Eph Nomenclature Committee (1997) based on their structures and sequence relationships. Ephrins are divided into the ephrin-A (EFNA) class, which are anchored to the membrane by a glycosylphosphatidylinositol linkage, and the ephrin-B (EFNB) class, which are transmembrane proteins. Ephrin-B ligands also contain an intracellular tail with highly conserved tyrosine residues and a PDZ-binding motif at the C-terminus.^[3] This tail functions as a mechanism for reverse signaling, where signaling occurs into the ligand-containing cell, as opposed to the cell with the receptor. Upon receptor-ligand interaction the tyrosine residues become phosphorylated and there is recruitment of PDZ domain-containing proteins.^[3] The Eph family of receptors are similarly divided into two groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands.^[2] EphrinB3 has been implicated in mediating various developmental events, particularly in the nervous system. EphrinB3 reverse signaling is important for axon pruning and synapse and spine formation during postnatal development of the nervous system.^{[4] [5]} Previous work has also shown that signaling through this ligand is important for radial migration during cortical development.^[4] Moreover, levels of EFNB3 expression are particularly high in several forebrain subregions compared to other brain subregions, and may play a pivotal role in forebrain function. It has been suggested that ephrinB3 signaling is necessary for synaptic plasticity to occur in the hippocampus; this implicates ephrinB3 as a major player in learning and memory.^[5] More recently, ephrinB3 has been shown to regulate proliferation of neural stem cells in the adult subventricular zone (SVZ).^{[4] [6]}

Further reading

• Flanagan JG, Vanderhaeghen P . The ephrins and Eph receptors in neural development. . Annu. Rev. Neurosci. . 21 . 309–45 . 1998 . 9530499 . 10.1146/annurev.neuro.21.1.309 .
• Zhou R . The Eph family receptors and ligands. . Pharmacol. Ther. . 77 . 3 . 151–81 . 1998 . 9576626 . 10.1016/S0163-7258(97)00112-5 .
• Holder N, Klein R . Eph receptors and ephrins: effectors of morphogenesis. . Development . 126 . 10 . 2033–44 . 1999 . 10.1242/dev.126.10.2033 . 10207129 .
• Wilkinson DG . Eph receptors and ephrins: regulators of guidance and assembly . Int. Rev. Cytol. . 196 . 177–244 . 2000 . 10730216 . 10.1016/S0074-7696(00)96005-4 . International Review of Cytology . 978-0-12-364600-2 .
• Xu Q, Mellitzer G, Wilkinson DG . Roles of Eph receptors and ephrins in segmental patterning . Philos. Trans. R. Soc. Lond. B Biol. Sci. . 355 . 1399 . 993–1002 . 2001 . 11128993 . 10.1098/rstb.2000.0635 . 1692797 .
• Wilkinson DG . Multiple roles of EPH receptors and ephrins in neural development . Nat. Rev. Neurosci. . 2 . 3 . 155–64 . 2001 . 11256076 . 10.1038/35058515 . 205014301 .
• Gale NW, Flenniken A, Compton DC . Elk-L3, a novel transmembrane ligand for the Eph family of receptor tyrosine kinases, expressed in embryonic floor plate, roof plate and hindbrain segments . Oncogene . 13 . 6 . 1343–52 . 1996 . 8808709 . etal.
• Ephnomenclaturecommittee. Unified nomenclature for Eph family receptors and their ligands, the ephrins. Eph Nomenclature Committee . Cell . 90 . 3 . 403–4 . 1997 . 9267020 . 10.1016/S0092-8674(00)80500-0 . 26773768 . free .
• Bergemann AD, Zhang L, Chiang MK . Ephrin-B3, a ligand for the receptor EphB3, expressed at the midline of the developing neural tube . Oncogene . 16 . 4 . 471–80 . 1998 . 9484836 . 10.1038/sj.onc.1201557 . etal. free .
• Brückner K, Pablo Labrador J, Scheiffele P . EphrinB ligands recruit GRIP family PDZ adaptor proteins into raft membrane microdomains . Neuron . 22 . 3 . 511–24 . 1999 . 10197531 . 10.1016/S0896-6273(00)80706-0 . etal. free .
• Liu W, Ahmad SA, Jung YD . Coexpression of ephrin-Bs and their receptors in colon carcinoma . Cancer . 94 . 4 . 934–9 . 2002 . 11920461 . 10.1002/cncr.10122 . 25734266 . etal. free .
• Takemoto M, Fukuda T, Sonoda R . Ephrin-B3-EphA4 interactions regulate the growth of specific thalamocortical axon populations in vitro . Eur. J. Neurosci. . 16 . 6 . 1168–72 . 2002 . 12383247 . 10.1046/j.1460-9568.2002.02166.x . 7540058 . etal.
• Strausberg RL, Feingold EA, Grouse LH . 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 . etal. free .

Notes and References

1. Tang XX, Pleasure DE, Ikegaki N . cDNA cloning, chromosomal localization, and expression pattern of EPLG8, a new member of the EPLG gene family encoding ligands of EPH-related protein-tyrosine kinase receptors . Genomics . 41 . 1 . 17–24 . May 1997 . 9126477 . 10.1006/geno.1997.4615 . free .
2. Web site: Entrez Gene: EFNB3 ephrin-B3.
3. Klein. Rudiger. Eph/ephrin signalling during development. Development. November 15, 2012. 10.1242/dev.074997. 23093422. 139. 22. 4105–9. free.
4. Rodger. Jennifer. Lorena Salvatore . Paolo Migani . Should I Stay or Should I Go? Ephs and Ephrins in Neuronal Migration. Neurosignals. 2012. 10.1159/000333784. 22456188. 20. 3. 190–201. free.
5. Hruska. Martin. Matthew B. Dalva. Ephrin regulation of synapse formation, function and plasticity. Molecular and Cellular Neuroscience. 2012. 10.1016/j.mcn.2012.03.004. 22449939. 50. 1. 35–44. 3631567.
6. Ricard. Jerome. Jessica Salinas . Lissette Garcia . Daniel J. Liebl . EphrinB3 regulates cell proliferation and survival in adult neurogenesis. Molecular and Cellular Neuroscience. 2006. 10.1016/j.mcn.2006.01.002. 16483793 . 31 . 4 . 713–22. 206830930.