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. 2018 Jun 5;27(17):3060–3078. doi: 10.1093/hmg/ddy215

Figure 2.

Figure 2.

Altered F-actin dynamics in LMNA cardiomyopathy. (A) Immunoblot from one representative experiment showing the effect of lamin A H222P on the amounts of G-actin and F-actin and the calculated F/G actin ratios. C2-H222P cells were either untreated (UT), or treated with cytochalasin D, jasplakinolide or selumetinib. Data are represented as means±SEM (n=3; **P <0.005, ***P <0.0005) from three independent repeats. (B) Microscopic analyses of F-actin depolymerization and/or severing. Micrographs show in vitro F-actin filaments alone or incubated in the presence of protein extracts from C2-WT or C2-H222P cells with or without selumetinib treatment. (C) Immunoblot from one representative experiment illustrating the effects of transfection with ERK2 and MEK1 constructs on the amount of G-actin and F-actin and the calculated F/G actin ratio. NT indicates not transfected. Data are represented as means±SEM (n=3; **P<0.005, ***P <0.0005) from three independent repeats. (D) Graph showing left ventricular fractional shortening (FS) in 3- and 6-month-old male LmnaH222P/H222P mice (Lmna H222P) (n=10) compared with Lmna+/+ (Lmna WT) (n=19) mice. The central line represents the median, the box limits the interquartile range and the whiskers the minimum and maximum (***P <0.0005). Immunoblot illustrating the effect of lamin A H222P on the amount of G-actin and F-actin and the calculated F/G actin ratio protein extracts of hearts from mice at 3 and 6 months of age. Data are represented as means±SEM (n=3; **P<0.005, ***P <0.0005) from three independent repeats. (E) Immunoblot of two representative experiments showing G-actin and F-actin and the calculated F/G actin ratio in protein extracts of hearts from LmnaH222P/H222P; Erk1+/+ mice (Lmna H222P) and LmnaH222P/H222P; Erk1-/- mice (Lmna H222P/Erk1 KO). Data are represented as means ± SEM (n=3; **P<0.005) from three independent repeats. (F) Immunoblot illustrating the amount of G-actin and F-actin and the calculated F/G actin ratio in hearts from unaffected subjects (WT) and from two patients with cardiomyopathy caused by LMNA mutation (LMNA mut).