title: Four and a half LIM protein 1C (FHL1C): a binding partner for voltage-gated potassium channel K(v1.5).
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.
authors: Institute of Human Genetics, Institute of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.
authors: Ivana
authors: I
authors: Poparic
authors: Wolfgang
authors: W
authors: Schreibmayer
authors: Benedikt
authors: B
authors: Schoser
authors: Gernot
authors: G
authors: Desoye
authors: Astrid
authors: A
authors: Gorischek
authors: Heidi
authors: H
authors: Miedl
authors: Sonja
authors: S
authors: Hochmeister
authors: Josepha
authors: J
authors: Binder
authors: Stefan
authors: S
authors: Quasthoff
authors: Klaus
authors: K
authors: Wagner
authors: Christian
authors: C
authors: Windpassinger
authors: Ernst
authors: E
authors: Malle
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016022:Case-Control Studies; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D040181:Genetic Diseases, X-Linked / Q000378:metabolism / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D015640:Ion Channel Gating; D007700:Kinetics; D051666:Kv1.5 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009133:Muscular Atrophy / Q000378:metabolism / Q000473:pathology; D050505:Mutant Proteins / Q000378:metabolism; D032446:Myoblasts / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013347:Subcellular Fractions / Q000378:metabolism; D014981:Xenopus; D014982:Xenopus laevis
chemical_list: C101149:FHL1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C496981:KCNA5 protein, human; D051666:Kv1.5 Potassium Channel; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D050505:Mutant Proteins; D020033:Protein Isoforms