Muscle Lim Protein and Myosin Binding Protein C form a complex regulating muscle differentiation

Publication date: Available online 1 September 2017
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Author(s): Demetrios A. Arvanitis, Elizabeth Vafiadaki, Vasiliki Papalouka, Despina Sanoudou
Muscle Lim Protein (MLP) is a protein with multiple functional roles in striated muscle physiology and pathophysiology. Herein, we demonstrate that MLP directly binds to slow, fast, and cardiac myosin-binding protein C (MyBP-C) during myogenesis, as shown by yeast two-hybrid, and a range of protein-protein interaction assays. The minimal interacting domains involve MLP inter-LIM and MyBP-C C4. The interaction is sensitive to cytosolic Ca²⁺ concentrations changes and to MyBP-C phosphorylation by PKA or CaMKII. Confocal microscopy of differentiating myoblasts showed MLP and MyBP-C colocalization during myoblast differentiation. Suppression of the complex formation with recombinant MyBP-C C4 peptide overexpression, inhibited myoblast differentiation by 65%. Suppression of both MLP and MyBP-C expression in myoblasts by siRNA revealed negative synergistic effects on differentiation. The MLP/MyBP-C complex modulates the actin activated myosin II ATPase activity in vitro, which could interfere with sarcomerogenesis and myofilaments assembly during differentiation. Our data demonstrate a critical role of the MLP/MyBP-C complex during early myoblast differentiation. Its absence in muscles with mutations or aberrant expression of MLP or MyBP-C could be directly implicated in the development of cardiac and skeletal myopathies.



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