Ca(2+)-dependent interaction between XXXX and calcineurin regulates activity of the Ca(2+) release channel in skeletal muscle.

@entity36464 @entity19 @entity19340 @entity30782 @entity70998
Calcineurin is a Ca(2+) and calmodulin-dependent protein phosphatase with diverse cellular functions. Here we examined the physical and functional interactions between calcineurin and @entity19340 ( @entity19340 ) in a C2C12 cell line derived from @entity19 skeletal muscle. Coimmunoprecipitation experiments revealed that the association between @entity19340 and calcineurin exhibits a strong Ca(2+) dependence. This association involves a Ca(2+) dependent interaction between calcineurin and FK506-binding protein ( @entity36464 ), an accessory subunit of @entity19340 . Pretreatment with cyclosporin A, an inhibitor of calcineurin, enhanced the caffeine-induced Ca(2+) release (CICR) in C2C12 cells. This effect was similar to those of FK506 and rapamycin, two drugs known to cause dissociation of @entity36464 from @entity19340 . Overexpression of a constitutively active form of calcineurin in C2C12 cells, DeltaCnA(391-521) (deletion of the last 131 amino acids from calcineurin), resulted in a decrease in CICR. This decrease in CICR activity was partially recovered by pretreatment with cyclosporin A. Furthermore, overexpression of an endogenous @entity30782 (cain) or an inactive form of calcineurin (DeltaCnA( @entity70998 )) in C2C12 cells resulted in up-regulation of CICR. Taken together, our data suggest that a trimeric-interaction among calcineurin, @entity36464 , and @entity19340 is important for the regulation of the @entity19340 channel activity and may play an important role in the Ca(2+) signaling of muscle contraction and relaxation.
