TY - JOUR T1 - Muscle Lim Protein and myosin binding protein C form a complex regulating muscle differentiation JF - Biochim Biophys Acta Mol Cell ResBiochim Biophys Acta Mol Cell ResBiochim Biophys Acta Mol Cell Res Y1 - 2017 A1 - Arvanitis, DA A1 - Vafiadaki, E. A1 - Papalouka, V. A1 - Sanoudou, D. KW - Adenosine Triphosphatases/genetics KW - Animals KW - Carrier Proteins/*genetics/metabolism KW - Cell Differentiation/*genetics KW - Gene Expression Regulation, Developmental KW - Humans KW - LIM Domain Proteins/*genetics/metabolism KW - Muscle Development/*genetics KW - Muscle Proteins/*genetics/metabolism KW - Muscle, Striated/growth & development/metabolism KW - Muscular Diseases/genetics/pathology KW - Myoblasts/metabolism KW - Phosphorylation KW - Sarcomeres/genetics AB - 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 Ca(2+) 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. VL - 1864 SN - 0167-4889 (Print)0167-4889 (Linking) N1 - Arvanitis, Demetrios AVafiadaki, ElizabethPapalouka, VasilikiSanoudou, DespinaengResearch Support, Non-U.S. Gov'tNetherlands2017/09/05 06:00Biochim Biophys Acta Mol Cell Res. 2017 Dec;1864(12):2308-2321. doi: 10.1016/j.bbamcr.2017.08.010. Epub 2017 Sep 1. JO - Biochimica et biophysica acta. Molecular cell researchBiochimica et biophysica acta. Molecular cell research ER -