Human muscle LIM protein dimerizes along the actin cytoskeleton and cross-links actin filaments.

  • Cytoskeleton and Cancer Progression
  • Cardiovascular Research Unit
August 15, 2014 By:
  • Hoffmann C
  • Moreau F
  • Moes M
  • Luthold C
  • Dieterle M
  • Goretti E
  • Neumann K
  • Steinmetz A
  • Thomas C.

The muscle LIM protein (MLP) is a nucleo-cytoplasmic shuttling protein playing important roles in the regulation of myocyte remodeling and adaptation to hypertrophic stimuli. Missense mutations in human MLP or its ablation in transgenic mice promote cardiomyopathy and heart failure. The exact function(s) of MLP in the cytoplasmic compartment and the underlying molecular mechanisms remain largely unknown. Here, we provide evidence that MLP autonomously binds to, stabilizes and bundles actin filaments independently of calcium and pH. Using total internal reflection fluorescence microscopy, we show how MLP crosslinks actin filaments into both unipolar and mixed polarity bundles. Quantitative analysis of the actin cytoskeleton configuration confirmed that MLP substantially promotes actin-bundling in live myoblasts. In addition, Bimolecular Fluorescence Complementation (BiFC) assays revealed MLP self-association. Remarkably, BiFC complexes mostly localize along actin filament-rich structures such as stress fibers and sarcomeres, supporting a functional link between MLP self-association and actin-crosslinking. Finally, we demonstrate that MLP self-associates through its N-terminal LIM domain whereas it binds to AFs through its C-terminal LIM domain. Together our data support that MLP contributes to the maintenance of cardiomyocyte cytoarchitecture by a mechanism involving its self-association and actin filament crosslinking.

2014 Aug. Mol Cell Biol.34(16):3053-65. Epub 2014 Jun 16.
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