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Four and a half LIM protein 1C (FHL1C): a binding partner for voltage-gated potassium channel K(v1.5).
- Source :
-
PloS one [PLoS One] 2011; Vol. 6 (10), pp. e26524. Date of Electronic Publication: 2011 Oct 28. - Publication Year :
- 2011
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 6
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 22053194
- Full Text :
- https://doi.org/10.1371/journal.pone.0026524