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8.A.197.  The Ephrin (Ephrin) Family 

Chromosome 13q deletions encompassing EFNB2, which encodes the transmembrane protein ephrin-B2 (216 aas and one N-terminal TMS), cause syndromic forms of sensorineural hearing loss. In the cochlea, adjacent non-sensory epithelial cells are connected via gap junction channels, the activities of which are critical to maintain cochlear homeostasis. Ephrin-B2 promotes the assembly of connexin 30 (Cx30) gap junction plaques (GJPs) between adjacent non-sensory Deiters' cells (Defourny et al. 2021). Ephrin-B2 preferentially interacts with Cx30 in the periphery of the GJPs, i.e. where newly synthesized connexin hemichannels accrue to the GJP. Heterozygous mice encoding an Efnb2 null allele display excessive clathrin-mediated internalization of Cx30 GJPs in early postnatal stages. Ectopic activation of ephrin-B2 reverse signalling promotes the internalization of Cx30 GJPs. Thus, a cell-autonomous, Eph receptor-independent role of ephrin-B2 in the assembly of Cx30 GJPs is suggested. Early GJP degradation could play a role in the pathogenic process leading to progressive sensorineural hearing loss due to Efnb2/EFNB2 haploinsufficiency (Defourny et al. 2021). There are many ephrins: Ephrin A1 - 7; B1 - 4.  These proteins play important roles in cancer and neurodegenerative diseases, and many review articles have been published on this subject. The EPH/ephrin system constitutes a bidirectional signaling pathway comprised of a family of tyrosine kinase receptors in tandem with their plasma membrane-bound ligands, the ephrins (Papadakos et al. 2022).  Homologs appear to exist only in animals.

References associated with 8.A.197 family:

Defourny, J., C. Audouard, A. Davy, and M. Thiry. (2021). Efnb2 haploinsufficiency induces early gap junction plaque disassembly and endocytosis in the cochlea. Brain Res Bull 174: 153-160. 34139316
Papadakos, S.P., L. Petrogiannopoulos, A. Pergaris, and S. Theocharis. (2022). The EPH/Ephrin System in Colorectal Cancer. Int J Mol Sci 23:. 35269901