Cofilin-1 phosphorylation catalyzed by ERK1/2 alters cardiac actin dynamics in dilated cardiomyopathy caused by lamin A/C gene mutation.

Autor: Chatzifrangkeskou M; Sorbonne Université, UPMC Paris 06, INSERM UMRS974, Center of Research in Myology, F-75013 Paris, France., Yadin D; Institute for Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany., Marais T; Sorbonne Université, UPMC Paris 06, INSERM UMRS974, Center of Research in Myology, F-75013 Paris, France., Chardonnet S; Sorbonne Université, UPMC Paris 06, INSERM, UMS29 Omique, F-75013 Paris, France., Cohen-Tannoudji M; Sorbonne Université, UPMC Paris 06, INSERM UMRS974, Center of Research in Myology, F-75013 Paris, France., Mougenot N; Sorbonne Université, UPMC Paris 06, INSERM, UMS28 Phénotypage du Petit Animal, Paris F-75013, France., Schmitt A; Institut Cochin, INSERM U1016-CNRS UMR 8104, Université Paris Descartes-Sorbonne Paris Cité, Paris F-75014, France., Crasto S; Istituto Clinico Humanitas IRCCS, Milan, Italy.; Istituto Ricerca Genetica e Biomedica, National Research Council of Italy, Milan 20089, Italy., Di Pasquale E; Istituto Clinico Humanitas IRCCS, Milan, Italy.; Istituto Ricerca Genetica e Biomedica, National Research Council of Italy, Milan 20089, Italy., Macquart C; Sorbonne Université, UPMC Paris 06, INSERM UMRS974, Center of Research in Myology, F-75013 Paris, France., Tanguy Y; Sorbonne Université, UPMC Paris 06, INSERM UMRS974, Center of Research in Myology, F-75013 Paris, France., Jebeniani I; Faculté de Médecine La Timone, Université Aix-Marseille, INSERM UMR910, Marseille 13005, France., Pucéat M; Faculté de Médecine La Timone, Université Aix-Marseille, INSERM UMR910, Marseille 13005, France., Morales Rodriguez B; Sorbonne Université, UPMC Paris 06, INSERM UMRS974, Center of Research in Myology, F-75013 Paris, France., Goldmann WH; Department of Physics, Friedrich-Alexander-University of Erlangen-Nuremberg, 91054 Erlangen, Germany., Dal Ferro M; Cardiovascular Department, Ospedali Riuniti and University of Trieste, Trieste, Italy., Biferi MG; Sorbonne Université, UPMC Paris 06, INSERM UMRS974, Center of Research in Myology, F-75013 Paris, France., Knaus P; Institute for Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany., Bonne G; Sorbonne Université, UPMC Paris 06, INSERM UMRS974, Center of Research in Myology, F-75013 Paris, France., Worman HJ; Department of Medicine.; Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA., Muchir A; Sorbonne Université, UPMC Paris 06, INSERM UMRS974, Center of Research in Myology, F-75013 Paris, France.
Jazyk: angličtina
Zdroj: Human molecular genetics [Hum Mol Genet] 2018 Sep 01; Vol. 27 (17), pp. 3060-3078.
DOI: 10.1093/hmg/ddy215
Abstrakt: Hyper-activation of extracellular signal-regulated kinase (ERK) 1/2 contributes to heart dysfunction in cardiomyopathy caused by mutations in the lamin A/C gene (LMNA cardiomyopathy). The mechanism of how this affects cardiac function is unknown. We show that active phosphorylated ERK1/2 directly binds to and catalyzes the phosphorylation of the actin depolymerizing factor cofilin-1 on Thr25. Cofilin-1 becomes active and disassembles actin filaments in a large array of cellular and animal models of LMNA cardiomyopathy. In vivo expression of cofilin-1, phosphorylated on Thr25 by endogenous ERK1/2 signaling, leads to alterations in left ventricular function and cardiac actin. These results demonstrate a novel role for cofilin-1 on actin dynamics in cardiac muscle and provide a rationale on how increased ERK1/2 signaling leads to LMNA cardiomyopathy.
Databáze: MEDLINE