Details

Autor(en) / Beteiligte

• Chatzifrangkeskou, Maria
• Yadin, David
• Marais, Thibaut
• Chardonnet, Solenne
• Cohen-Tannoudji, Mathilde
• Mougenot, Nathalie
• Schmitt, Alain
• Crasto, Silvia
• Di Pasquale, Elisa
• Macquart, Coline
• Tanguy, Yannick
• Jebeniani, Imen
• Pucéat, Michel
• Morales Rodriguez, Blanca
• Goldmann, Wolfgang H
• Dal Ferro, Matteo
• Biferi, Maria-Grazia
• Knaus, Petra
• Bonne, Gisèle
• Worman, Howard J
• Muchir, Antoine

Titel

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

Ist Teil von

• Human molecular genetics, 2018-09, Vol.27 (17), p.3060-3078

Ort / Verlag

England: Oxford University Press

Erscheinungsjahr

2018

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Abstract 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.