Endogenous calpain-3 activation is primarily governed by small increases in resting cytoplasmic [Ca2+] and is not dependent on stretch.

ABSTRACT: Proteolytically active calpain-3/p94 is clearly vital for normal muscle function, since its absence leads to limb girdle muscular dystrophy 2A, but its function and regulatory control are poorly understood. Here we use single muscle fibers, individually skinned by microdissection, to investigate the diffusibility and autolytic activation of calpain-3 in situ. Virtually all calpain-3 present in mature muscle fibers is tightly bound in the vicinity of the titin N2A line and triad junctions and remains so irrespective of fiber stretching or raised [Ca(2+)]. Most calpain-3 is evidently bound within the contractile filament lattice, because (i) its slow diffusional loss is slowed further by locking myosin and actin into rigor and (ii) detergent dispersion of membranes causes rapid washout of mo

SUBMITTER: Murphy RM 

PROVIDER: S-EPMC2658075 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature