Proteomic analysis of the developing mammalian brain links PCDH19 to the Wnt/β-catenin signalling pathway
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(Published version)
Date
2024
Authors
de Nys, R.
Gardner, A.E.
van Eyk, C.
Tasheva, S.
Thomas, P.Q.
Bhattacharjee, R.
Jolly, L.
Martinez-Garay, I.
Fox, I.W.J.
Kamath, K.S.
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Journal article
Citation
Molecular Psychiatry, 2024; 29(7):2199-2210
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Rebekah de Nys, Alison Gardner, Clare van Eyk, Stefka Mincheva-Tasheva, Paul Thomas, Rudrarup Bhattacharjee, Lachlan Jolly, Isabel Martinez-Garay, Ian W. J. Fox, Karthik Shantharam Kamath, Raman Kumar and Jozef Gecz
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Abstract
Clustering Epilepsy (CE) is a neurological disorder caused by pathogenic variants of the Protocadherin 19 (PCDH19) gene. PCDH19 encodes a protein involved in cell adhesion and Estrogen Receptor α mediated-gene regulation. To gain further insights into the molecular role of PCDH19 in the brain, we investigated the PCDH19 interactome in the developing mouse hippocampus and cortex. Combined with a meta-analysis of all reported PCDH19 interacting proteins, our results show that PCDH19 interacts with proteins involved in actin, microtubule, and gene regulation. We report CAPZA1, αN-catenin and, importantly, β-catenin as novel PCDH19 interacting proteins. Furthermore, we show that PCDH19 is a regulator of β-catenin transcriptional activity, and that this pathway is disrupted in CE individuals. Overall, our results support the involvement of PCDH19 in the cytoskeletal network and point to signalling pathways where PCDH19 plays critical roles.
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Published online: 07 March 2024
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© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creativecommons.org/licenses/by/4.0/.