EphA4-ADAM10 Interplay Patterns the Cochlear Sensory Epithelium through Local Disruption of Adherens Junctions.

[en] The cochlear sensory epithelium contains a functionally important triangular fluid-filled space between adjacent pillar cells referred to as the tunnel of Corti. However, the molecular mechanisms leading to local cell-cell separation during development remain elusive. Here we show that EphA4 associates with ADAM10 to promote the destruction of E-cadherin-based adhesions between adjacent pillar cells. These cells fail to separate from each other, and E-cadherin abnormally persists at the pillar cell junction in EphA4 forward-signaling-deficient mice, as well as in the presence of ADAM10 inhibitor. Using immunolabeling and an in situ proximity ligation assay, we found that EphA4 forms a complex with E-cadherin and its sheddase ADAM10, which could be activated by ephrin-B2 across the pillar cell junction to trigger the cleavage of E-cadherin. Altogether, our findings provide a new molecular insight into the regulation of adherens junctions, which might be extended to a variety of physiological or pathological processes.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

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

Peuckert, Christiane

Kullander, Klas

Malgrange, Brigitte ; Université de Liège - ULiège > Developmental Neurobiology

Language :

English

Title :

EphA4-ADAM10 Interplay Patterns the Cochlear Sensory Epithelium through Local Disruption of Adherens Junctions.

Publication date :

2019

Journal title :

iScience

eISSN :

2589-0042

Publisher :

Elsevier, Cambridge, United States - Massachusetts

Volume :

Pages :

246-257

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Available on ORBi :

since 16 January 2019

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Bibliography

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