Calsarcins, a novel family of sarcomeric calcineurin-binding proteins.
The calcium- and calmodulin-dependent protein phosphatase calcineurin has been implicated in the transduction of signals that control the hypertrophy of cardiac muscle and slow fiber gene expression in skeletal muscle. To identify proteins that mediate the effects of calcineurin on striated muscles, we used the calcineurin catalytic subunit in a two-hybrid screen for cardiac calcineurin-interacting proteins. From this screen, we discovered a member 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 expressed in developing cardiac and skeletal muscle during embryogenesis, but calsarcin-1 is expressed specifically in adult cardiac and slow-twitch skeletal muscle, whereas calsarcin-2 is restricted to fast skeletal muscle. Calsarcins represent a novel family of sarcomeric proteins that link calcineurin with the contractile apparatus, thereby potentially coupling muscle activity to calcineurin activation.
Frey
N
N
Departments of Molecular Biology and Pathology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-9148, USA.
Richardson
J A
JA
Olson
E N
EN
D000185:Actinin / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary; D015870:Gene Expression; D006321:Heart / Q000196:embryology; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011817:Rabbits; D012518:Sarcomeres / Q000378:metabolism; D013997:Time Factors
D002352:Carrier Proteins; D018076:DNA, Complementary; C419780:MYOZ1 protein, human; C419779:MYOZ2 protein, human; D009124:Muscle Proteins; D000185:Actinin; D019703:Calcineurin