Fig. 6: α-Tubulin acetylation mediates Cx43 localization in cellular and mouse models expressing cardiomyopathy-causing mutant A-type lamins. | Nature Communications

Fig. 6: α-Tubulin acetylation mediates Cx43 localization in cellular and mouse models expressing cardiomyopathy-causing mutant A-type lamins.

From: Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations

Fig. 6

a, b Immunofluorescence staining of Cx43 and α-actinin in a isolated adult cardiomyocytes and b heart cross-sections from 3-month-old male WT mice and Lmnap.H222P/H222P (H222P) mice. The arrows indicate the lateralization of Cx43. c Immunofluorescence staining of Cx43 and N-cadherin in C2-WT and C2-H222P cells. d Immunofluorescence staining of Cx43 in C2-WT and C2-H222P cells organized in 3D spheroids. e, f Top: immunoblot showing expression of acetylated and total α-tubulin in e C2C12 cells treated or not with siRNA targeting Atat1 and f in C2-H222P cells treated or not with different doses of tubastatin A. GAPDH was used as a loading control. e, f Bottom: representative immunofluorescence staining of Cx43 and acetylated α-tubulin in e C2-H222P cells treated or not with a siRNA targeting Atat1 and f in C2-H222P cells treated or not with tubastatin A. The insets show a higher magnification. g Immunofluorescence staining of Cx43 and α-actinin of heart cross-sections from 6-month-old male Atat1+/+ (WT) mice and Atat1 knockout mice (Atat1−/−) (top panel); from 5-month-old male WT mice transduced or not with AAV expressing HDAC6 (middle panel) and from 3-month-old male Lmnap.H222P/H222P (H222P) mice treated with tubastatin A compared with mice treated with DMSO (bottom panel). h Bar graph showing the quantification of lateralized Cx43 staining (n = 4 mice per condition; mean ± SD). i Left: representative Sirius red staining of heart cross-sections from 6-month-old male Atat1+/+ (WT) mice, Atat1 knockout mice (Atat1−/−), and 3-month-old male Lmnap.H222P/H222P (H222P) mice treated or not with tubastatin A. Right: bar graph showing the quantification of Sirius red-stained area (n = 4 mice per condition; mean ± SD). For a–g, nuclei counterstained with DAPI are shown and a representative of three independent repeats is shown. Statistics: for h and i, one-way ANOVA followed by Tukey’s multiple comparison test. Source data are provided as a Source Data file.

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