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Calpain 1-gamma filamin interaction in muscle cells : a possible in situ regulation by PKC-alpha
(2006)
Calpain 1-gamma filamin interaction in muscle cells :a possible in situ regulation by PKC-alpha
(2006)
Calpain 1-gamma filamin interaction in muscle cells : a possible in situ regulation by PKC-alpha
(2006)
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 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.
Der Beitrag erinnert an das wechselvolle Leben des Friedensnobelpreisträgers Henry Dunant, sucht nach biografischen Wurzeln seines von Menschlichkeit und Würde getragenen Verhaltens und macht auf seine Leistungen aufmerksam. Er will aber auch die Frage nach der Bedeutung des humanitären Völkerrechts im Verhältnis von Krieg und Frieden nicht außer Acht lassen.