Calpain 1-gamma filamin interaction in muscle cells : a possible in situ regulation by PKC-alpha
- Calpains are a family of calcium-dependant cysteine-proteases involved in cytoskeleton remodelling and muscle differentiation. In a recent study, we observed the presence of calpain I in the muscle contractile apparatus and specifically in the N1- and N2-fines. This calpain isoform was found to be involved in the degradation of muscle fibres via proteolysis of key proteins in Z-disk and costameric junctions. The goal of this study was to determine whether gamma-filamin - a specific muscle isoform of the filamin family - is a calpain, I substrate and to characterise this interaction. gamma-Filamin is a major muscle architectural protein located in the Z-fine and under the sarcolemmal membrane. This protein is a component of the chain binding the sarcolemma to the sarcomeric structure. In this study, we found that gamma-filamin formed a stable complex in vitro and in cells with calpain I in the absence of calcium stimulation. We also located the binding domains in the C-terminus of gamma-filamin with a cleavage site between serine 2626Calpains are a family of calcium-dependant cysteine-proteases involved in cytoskeleton remodelling and muscle differentiation. In a recent study, we observed the presence of calpain I in the muscle contractile apparatus and specifically in the N1- and N2-fines. This calpain isoform was found to be involved in the degradation of muscle fibres via proteolysis of key proteins in Z-disk and costameric junctions. The goal of this study was to determine whether gamma-filamin - a specific muscle isoform of the filamin family - is a calpain, I substrate and to characterise this interaction. gamma-Filamin is a major muscle architectural protein located in the Z-fine and under the sarcolemmal membrane. This protein is a component of the chain binding the sarcolemma to the sarcomeric structure. In this study, we found that gamma-filamin formed a stable complex in vitro and in cells with calpain I in the absence of calcium stimulation. We also located the binding domains in the C-terminus of gamma-filamin with a cleavage site between serine 2626 and serine 2627 in the hinge 2 region. The catalytic (80 kDa) and regulatory (28 kDa) subunits of calpain I are both involved in high affinity binding at gamma-filamin. Moreover, we showed that phosphorylation of the filamin C- terminus domain by PKC alpha protected gamma-filamin against proteolysis by calpain I in COS cells. Stimulation of PKC activity in myotubes, prevented gamma-filamin proteolysis by calpain and resulted in an increase in myotube adhesion.…
Author details: | Fabrice Raynaud, Carole Jond-Necand, Anne Marcilhac, Dieter Fürst, Yves Benyamin |
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URL: | http://www.sciencedirect.com/science/journal/13572725 |
DOI: | https://doi.org/10.1016/j.biocel.2005.09.020 |
ISSN: | 1357-2725 |
Publication type: | Article |
Language: | English |
Year of first publication: | 2006 |
Publication year: | 2006 |
Release date: | 2017/03/24 |
Source: | International journal of biochemistry & cell biology. - ISSN 1357-2725. - 38 (2006), 3, S. 404 - 413 |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
Peer review: | Referiert |