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

Céline Hoffmann, Flora Moreau, Michèle Moes, Carole Luthold, Monika Dieterle, Emeline Goretti, Katrin Neumann, André Steinmetz, Clément Thomas*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

35 Citations (Scopus)

Abstract

The muscle LIM protein (MLP) is a nucleocytoplasmic 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 promotes 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 (AFs) independently of calcium and pH. Using total internal reflection fluorescence microscopy, we have shown how MLP cross-links 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 cross-linking. Finally, we have demonstrated 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 cross-linking.

Original languageEnglish
Pages (from-to)3053-3065
Number of pages13
JournalMolecular and Cellular Biology
Volume34
Issue number16
DOIs
Publication statusPublished - 2014

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