Efnb2 haploinsufficiency induces early gap junction plaque disassembly and endocytosis in the cochlea.

[en] Chromosome 13q deletions encompassing EFNB2, which encodes the transmembrane protein ephrin-B2, are likely to cause syndromic forms of sensorineural hearing loss of unclear origin. Thus, unravelling the pathogenic mechanisms could help to improve therapeutic strategies. In the cochlea, adjacent non-sensory epithelial cells are connected via gap junction channels, the activity of which is critical to maintain cochlear homeostasis. Here we show that ephrin-B2 promotes the assembly of connexin 30 (Cx30) gap junction plaques (GJPs) between adjacent non-sensory Deiters' cells. An in situ proximity ligation assay revealed that ephrin-B2 preferentially interacts with Cx30 in the periphery of the GJPs, i.e. where newly synthesized connexin hemichannels accrue to the GJP. Moreover, we observed that heterozygous mice encoding an Efnb2 null allele display excessive clathrin-mediated internalization of Cx30 GJPs in early postnatal stages. Finally, an in vitro organotypic assay revealed that ectopic activation of ephrin-B2 reverse signalling promotes the internalization of Cx30 GJPs. These data argue in favor of a cell-autonomous, Eph receptor-independent role of ephrin-B2 in the assembly of Cx30 GJPs. According to recent observations, early GJP degradation could certainly play a role in the pathogenic process leading to progressive sensorineural hearing loss due to Efnb2/EFNB2 haploinsufficiency.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Defourny, Jean ; Université de Liège - ULiège > GIGA Neurosciences - Cellular and tissular biology

Audouard, Christophe; Université de Toulouse > Centre de Biologie du Développement - Centre de Biologie Intégrative

Davy, Alice; Université de Toulouse > Centre de Biologie du Développement - Centre de Biologie Intégrative

Thiry, Marc ; Université de Liège - ULiège > Département des sciences de la vie > Biologie cellulaire

Language :

English

Title :

Efnb2 haploinsufficiency induces early gap junction plaque disassembly and endocytosis in the cochlea.

Publication date :

2021

Journal title :

Brain Research Bulletin

ISSN :

0361-9230

eISSN :

1873-2747

Publisher :

Elsevier, Netherlands

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Available on ORBi :

since 18 June 2021

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