Proteomic analysis of the developing mammalian brain links PCDH19 to the Wnt/β-catenin signalling pathway

de Nys, Rebekah, Gardner, Alison, van Eyk, Clare, Mincheva-Tasheva, Stefka, Thomas, Paul, Bhattacharjee, Rudrarup, Jolly, Lachlan, Martinez-Garay, Isabel ORCID: https://orcid.org/0000-0001-6849-7496, Fox, Ian W. J., Kamath, Karthik Shantharam, Kumar, Raman and Gecz, Jozef 2024. Proteomic analysis of the developing mammalian brain links PCDH19 to the Wnt/β-catenin signalling pathway. Molecular Psychiatry 10.1038/s41380-024-02482-z

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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.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Biosciences
Publisher:	Springer Nature [academic journals on nature.com]
ISSN:	1359-4184
Date of First Compliant Deposit:	19 March 2024
Date of Acceptance:	7 February 2024
Last Modified:	20 Mar 2024 14:46
URI:	https://orca.cardiff.ac.uk/id/eprint/167352

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