Thesis defense Cyrielle Jajkiewicz
  • Le 20 February 2024
    Amphi DE
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  • 14h

Title of the thesis : Role of Rad protein in the pathophysiology of Brugada syndrome


Team II - Ion channels and cardiopathies

Directeur de thèse

Flavien Charpentier


Mickaël Derangeon


Elise Balse, Maître de conférence des universités , UMR1166 Université Pierre et Marie Curie
Francesca Rochais, Chargée de recherche, Marseille Medical Geneteics


Nicolas Bourmeyster, PU-PH, laboratoire 4CS, Poitiers
Nathalie Gaborit, Chargée de recherche, l'Institut du thorax, Inserm UMR 1087/CNRS UMR 6291


The protein Rad (Ras-associated with diabetes), a member of the RGK family, plays a crucial role in regulating cardiac function by directly interacting with Cavβ, a subunit of the voltage-gated L-type calcium channel complex. The RRAD gene, responsible for synthesizing this protein, has been identified in a family affected by Brugada syndrome, all carrying the p.R211H variant. This syndrome is an inherited cardiac rhythm disorder that can lead to ventricular fibrillations and sudden cardiac death. The aim of this study is to assess the impact of the Rad protein in the development of Brugada syndrome in individuals carrying the p.R211H variant.This involves characterizing the effects of the mutation on electrical activity and cardiac structure in mice with an equivalent mutation (p.R210H) and exploring the molecular mechanisms of Rad regulating the Nav1.5 sodium channel. The results demonstrate that Rad R211H induces a reduction in the protein expression of Rad, Nav1.5, and Cx43, accompanied by a relocation of these proteins, contributing to electrical disturbances. This study represents the first evidence that Rad is part of a macromolecular complex including Nav1.5 and Cx43, and its presence increases the membrane expression of Nav1.5.

Mis à jour le 11 January 2024.