Cochlear connexin 30 homomeric and heteromeric channels exhibit distinct assembly mechanisms.

[en] Many of the mutations in GJB2 and GJB6, which encode connexins 26 and 30 (Cx26 and Cx30), impair the formation of membrane channels and cause autosomal syndromic and non-syndromic hearing loss. In cochlear non-sensory supporting cells, Cx26 and Cx30 form two types of homomeric and heteromeric gap junctions. The biogenesis processes of these channels occurring in situ remain largely unknown. Here we show that Cx30 homomeric and Cx26/Cx30 heteromeric gap junctions exhibit distinct assembly mechanisms in the cochlea. When expressed as homomeric channels, Cx30 preferentially interacts with beta-actin in the peripheral non-junctional membrane region, called perinexus, and strongly relies on the actin network for gap junction plaque assembly. In contrast, we found that Cx26/Cx30 heteromeric gap junction plaques are devoid of perinexus and associated actin network, and resist to actin-depolymerizating drug. This supports that Cx26/Cx30 oligomers could be directly delivered from the interior of the cell to the junctional plaque. Altogether, our data provide a novel insight in homomeric and heteromeric gap junction plaque assembly in the cochlea.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Defourny, Jean ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie cellulaire

Thelen, Nicolas ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie cellulaire

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

Language :

English

Title :

Cochlear connexin 30 homomeric and heteromeric channels exhibit distinct assembly mechanisms.

Publication date :

2019

Journal title :

Mechanisms of Development

ISSN :

0925-4773

eISSN :

1872-6356

Publisher :

Elsevier, Netherlands

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Available on ORBi :

since 22 October 2018

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