Calsarcins, a novel family of sarcomeric calcineurin-binding proteins

The calcium- and calmodulin-dependent protein phosphatase calcineurin has b een implicated in the transduction of signals that control the hypertrophy of cardiac muscle and slow fiber gene expression in skeletal muscle. To ide ntify proteins that mediate the effects of calcineurin on striated muscles, we used the calcineurin catalytic subunit in a two-hybrid screen for cardi ac calcineurin-interacting proteins. From this screen, we discovered a memb er of a novel family of calcineurin-interacting proteins, termed calsarcins , which tether calcineurin to alpha -actinin at the z-line of the sarcomere of cardiac and skeletal muscle cells. Calsarcin-1 and calsarcin-2 are expr essed in developing cardiac and skeletal muscle during embryogenesis, but c alsarcin-1 is expressed specifically in adult cardiac and slow-twitch skele tal muscle, whereas calsarcin-2 is restricted to fast skeletal muscle. Cals arcins represent a novel family of sarcomeric proteins that link calcineuri n with the contractile apparatus, thereby potentially coupling muscle activ ity to calcineurin activation.