1. Four and a half LIM protein 1C (FHL1C): a binding partner for voltage-gated potassium channel K(v1.5).
- Author
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Poparic I, Schreibmayer W, Schoser B, Desoye G, Gorischek A, Miedl H, Hochmeister S, Binder J, Quasthoff S, Wagner K, Windpassinger C, and Malle E
- Subjects
- Animals, Blotting, Western, Case-Control Studies, Cell Cycle, Cell Line, Cell Proliferation, Genetic Diseases, X-Linked metabolism, Genetic Diseases, X-Linked pathology, Humans, Intracellular Signaling Peptides and Proteins genetics, Ion Channel Gating, Kinetics, Kv1.5 Potassium Channel genetics, LIM Domain Proteins genetics, Male, Mice, Muscle Proteins genetics, Muscular Atrophy metabolism, Muscular Atrophy pathology, Mutant Proteins metabolism, Myoblasts metabolism, Myoblasts pathology, Protein Binding, Protein Isoforms genetics, Protein Isoforms metabolism, Protein Transport, Reverse Transcriptase Polymerase Chain Reaction, Subcellular Fractions metabolism, Xenopus, Xenopus laevis, Intracellular Signaling Peptides and Proteins metabolism, Kv1.5 Potassium Channel metabolism, LIM Domain Proteins metabolism, Muscle Proteins metabolism
- Abstract
Four-and-a-half LIM domain protein 1 isoform A (FHL1A) is predominantly expressed in skeletal and cardiac muscle. Mutations in the FHL1 gene are causative for several types of hereditary myopathies including X-linked myopathy with postural muscle atrophy (XMPMA). We here studied myoblasts from XMPMA patients. We found that functional FHL1A protein is completely absent in patient myoblasts. In parallel, expression of FHL1C is either unaffected or increased. Furthermore, a decreased proliferation rate of XMPMA myoblasts compared to controls was observed but an increased number of XMPMA myoblasts was found in the G(0)/G(1) phase. Furthermore, low expression of K(v1.5), a voltage-gated potassium channel known to alter myoblast proliferation during the G(1) phase and to control repolarization of action potential, was detected. In order to substantiate a possible relation between K(v1.5) and FHL1C, a pull-down assay was performed. A physical and direct interaction of both proteins was observed in vitro. In addition, confocal microscopy revealed substantial colocalization of FHL1C and K(v1.5) within atrial cells, supporting a possible interaction between both proteins in vivo. Two-electrode voltage clamp experiments demonstrated that coexpression of K(v1.5) with FHL1C in Xenopus laevis oocytes markedly reduced K(+) currents when compared to oocytes expressing K(v1.5) only. We here present the first evidence on a biological relevance of FHL1C.
- Published
- 2011
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