Details

Autor(en) / Beteiligte

• Poparic, Ivana
• Schreibmayer, Wolfgang
• Schoser, Benedikt
• Desoye, Gernot
• Gorischek, Astrid
• Miedl, Heidi
• Hochmeister, Sonja
• Binder, Josepha
• Quasthoff, Stefan
• Wagner, Klaus
• Windpassinger, Christian
• Malle, Ernst
• Uversky, Vladimir N.

Titel

Four and a Half LIM Protein 1C (FHL1C): A Binding Partner for Voltage-Gated Potassium Channel Kv1.5

Ist Teil von

• PloS one, 2011-10, Vol.6 (10), p.e26524

Ort / Verlag

San Francisco: Public Library of Science

Erscheinungsjahr

2011

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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 G0/G1 phase. Furthermore, low expression of Kv1.5, a voltage-gated potassium channel known to alter myoblast proliferation during the G1 phase and to control repolarization of action potential, was detected. In order to substantiate a possible relation between Kv1.5 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 Kv1.5 within atrial cells, supporting a possible interaction between both proteins in vivo. Two-electrode voltage clamp experiments demonstrated that coexpression of Kv1.5 with FHL1C in Xenopus laevis oocytes markedly reduced K+ currents when compared to oocytes expressing Kv1.5 only. We here present the first evidence on a biological relevance of FHL1C.