Alternative titles; symbols
HGNC Approved Gene Symbol: EFNB3
Cytogenetic location: 17p13.1 Genomic coordinates (GRCh38): 17:7,705,202-7,711,372 (from NCBI)
Members of the ephrin family are ligands for EPH-related receptor tyrosine kinases and are attached to the cell membrane by either a glycosylphosphatidylinositol linkage or a single transmembrane domain. See 179610 for additional information on ephrins and the Eph receptor family.
Tang et al. (1997) isolated a cDNA encoding ephrin-B3 (EFNB3), named LERK8 by them, by screening a human fetal brain cDNA library using mouse Efnb1 cDNA as a probe. The EFNB3 protein contains a predicted transmembrane region, and its 340-amino acid sequence shares 38% and 40% identity with those of the transmembrane ephrins EFNB1 (300035) and EFNB2 (600527), respectively. Since the N-terminal halves of EFNB1, EFNB2, and EFNB3 are especially conserved, Tang et al. (1997) suggested that these proteins bind the same subclass of EPH-related receptor tyrosine kinases. In addition, a C-terminal region containing 5 conserved tyrosine residues is strikingly similar among these ephrins, and the authors speculated that this region may function in signal transduction. Using Northern blot analysis, Tang et al. (1997) found that the EFNB3 gene is expressed as a major 3.5-kb transcript. In the midterm fetus, the highest EFNB3 mRNA level is in brain, followed by heart, kidney, and lung; expression in the adult is restricted to brain and is particularly high in forebrain subregions. Tang et al. (1997) suggested that EFNB3 is important in both brain development and maintenance and that it may play a pivotal role in forebrain function.
Palmer et al. (2002) showed that SRC family kinases, or SFKs (see SRC; 190090), are positive regulators of ephrin-B phosphorylation and phosphotyrosine-mediated reverse signaling. EphB receptor engagement of ephrin-B caused rapid recruitment of SFKs to ephrin-B expression domains and transient SFK activation. With delayed kinetics, ephrin-B ligands recruited the cytoplasmic PDZ domain-containing protein tyrosine phosphatase PTPBL (see 600267) and were dephosphorylated. These data suggested the presence of a switch mechanism that allows a shift from phosphotyrosine-/SFK-dependent signaling to PDZ-dependent signaling.
Local circuits in the spinal cord that generate locomotion are termed central pattern generators. These provide coordinated bilateral control over the normal limb alternation that underlies walking. Isolated spinal cords from mice lacking either the EphA4 receptor (602188) or its ligand ephrin B3 have lost left-right limb alternation and instead exhibit synchrony. Kullander et al. (2003) identified EphA4-positive neurons as an excitatory component of the locomotor central pattern generator. Kullander et al. (2003) concluded that dramatic locomotor changes can occur as a consequence of local genetic rewiring and identified genes required for the development of normal locomotor behavior.
In mouse hippocampal neurons, Grunwald et al. (2004) showed that ephrin B2 and B3 are predominantly located postsynaptically and are required for synaptic plasticity, including both long-term potentiation and long-term depression. The EphA4 receptor is also critically involved in long-term plasticity independent of its cytoplasmic domain, suggesting that the ephrin B proteins are the active signaling partner. Grunwald et al. (2004) suggested that ephrins can be used in converse manners, depending on the synaptic site.
Tang et al. (1997) mapped the EFNB3 gene to chromosome 17 by PCR screening of somatic cell hybrid DNAs. They refined the localization to 17p13.1-p11.2 by PCR screening of a chromosome 17 regional mapping panel.
Grunwald, I. C., Korte, M., Adelmann, G., Plueck, A., Kullander, K., Adams, R. H., Frotscher, M., Bonhoeffer, T., Klein, R. Hippocampal plasticity requires postsynaptic ephrinBs. Nature Neurosci. 7: 33-40, 2004. [PubMed: 14699416] [Full Text: https://doi.org/10.1038/nn1164]
Kullander, K., Butt, S. J. B., Lebret, J. M., Lundfald, L., Restrepo, C. E., Rydstrom, A., Klein, R., Kiehn, O. Role of EphA4 and ephrinB3 in local neuronal circuits that control walking. Science 299: 1889-1892, 2003. [PubMed: 12649481] [Full Text: https://doi.org/10.1126/science.1079641]
Palmer, A., Zimmer, M., Erdmann, K. S., Eulenburg, V., Porthin, A., Heumann, R., Deutsch, U., Klein, R. EphrinB phosphorylation and reverse signaling: regulation by Src kinases and PTP-BL phosphatase. Molec. Cell 9: 725-737, 2002. [PubMed: 11983165] [Full Text: https://doi.org/10.1016/s1097-2765(02)00488-4]
Tang, X. X., Pleasure, D. E., 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: 17-24, 1997. [PubMed: 9126477] [Full Text: https://doi.org/10.1006/geno.1997.4615]