I am investigating the role of ion channels linked to heart disorders. I mainly focus on one ion channel, the calcium channel Cav1.2.
During my scientific carrier started in 2002, I have investigated different aspects of several important cardiac ion channels involved in the generation of the cardiac action potential, with a strong focus on Nav1.5 and Cav1.2. We have shown the Nedd4-dependent negative regulation of Nav1.5 and Cav1.2 channels. In addition, we also demonstrated that the counterpart of Nedd4-1, USP2-45, regulated Cav1.2 channel. We have highlighted the regulation of Nav1.5 channel via the syntrophin/dystrophin/utrophin complex in mouse ventricular cardiomyocytes. We reported also the regulation of cardiac Ca2+ and Na+ currents by mineralo- and glucocorticoids and the implication of the mutated auxiliary subunit of Cav channel, Cavα2-δ1, in a new type of cardiac pathology: The short QT syndrome type 6 (SQT6). Finally, we reported the role in vivo of different members of the Membrane-Associated GUanylate Kinase (MAGUK) family: the Synapse-Associated Protein-97 (SAP-97) and the Calcium/calmodulin-dependent Serine protein Kinase (CASK) into the regulation of the voltage gated sodium channel Nav1.5.
For the future, I plan on investigating voltage-gated calcium channel and the role of its auxiliary subunits.
On the Web
Blancard M, Debbiche A, Kato K, Cardin C, Sabrina G, Gandjbakhch E, Probst V, Haissaguerre M, Extramiana F, Hocini M, Olivier G, Leenhardt A, Guicheney P, Rougier JS. An African loss-of-function CACNA1C variant p.T1787M associated with a risk of ventricular fibrillation. Sci Rep. 2018. Oct 2;8(1):14619. doi: 10.1038/s41598-018-32867-4
Nafzger S, Rougier JS. Calcium/calmodulin-dependent serine protein kinase CASK modulates the L-type calcium current. Cell Calcium. 2017. Jan;61:10-21. doi: 10.1016/j.ceca.2016.10.001
Rougier JS*, Albesa M*, Syam N, Halet G, Abriel H, Viard P. Ubiquitin-specific protease USP2-45 acts as a molecular switch to promote α2δ-1-induced downregulation of Cav1.2 channels. Pflugers Arch. 2015. *(contributed equally). Sep;467(9):1919-29. doi: 10.1007/s00424-014-1636-6
Templin C*, Ghadri JR*, Rougier JS*, Baumer A, Kaplan V, Albesa M, Sticht H, Rauch A, Puleo C, Hu D, Barajas-Martinez H, Antzelevitch C, Lüscher TF, Abriel H, Duru F. Identification of a novel loss-of-function calcium channel gene mutation in short QT syndrome (SQTS6). Eur Heart J. 2011. *(contributed equally). May;32(9):1077-88. doi: 10.1093/eurheartj/ehr076
Rougier JS, Albesa M, Abriel H, Viard P. Neuronal Precursor Cell-expressed Developmentally Down-regulated 4-1 (NEDD4-1) Controls the Sorting of Newly Synthesized Cav1.2 Calcium Channels. J Biol Chem. 2011. Mar 18;286(11):8829-38. doi: 10.1074/jbc.M110.166520