A novel variant of cardiac myosin-binding protein-C that is unable to assemble into sarcomeres is expressed in the aged mouse atrium.
Cardiac myosin-binding protein-C (MyBP-C), also known as C-protein, is one of the major myosin-binding proteins localizing at A-bands. MyBP-C has three isoforms encoded by three distinct genes: fast-skeletal, slow-skeletal, and cardiac type. Herein, we are reporting a novel alternative spliced form of cardiac MyBP-C, MyBP-C(+), which includes an extra 30 nucleotides, encoding 10 amino acids in the carboxyl-terminal connectin/titin binding region. This alternative spliced form of MyBP-C(+) has a markedly decreased binding affinity to myosin filaments and connectin/titin in vitro and does not localize to A-bands in cardiac myocytes. When MyBP-C(+) was expressed in chicken cardiac myocytes, sarcomere structure was markedly disorganized, suggesting it has possible dominant negative effects on sarcomere organization. Expression of MyBP-C(+) is hardly detected in ventricles through cardiac development, but its expression gradually increases in atria and becomes the dominant form after 6 mo of age. The present study demonstrates an age-induced new isoform of cardiac MyBP-C harboring possible dominant negative effects on sarcomere assembly.
Sato
Naruki
N
Department of Biology, Faculty of Science, Chiba University, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
Kawakami
Tsutomu
T
Nakayama
Ayako
A
Suzuki
Hiroyuki
H
Kasahara
Hideko
H
Obinata
Takashi
T
D000375:Aging; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D003001:Cloning, Molecular; D006321:Heart / Q000196:embryology; D006325:Heart Atria / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism / Q000502:physiology; D012518:Sarcomeres / Q000235:genetics* / Q000378:metabolism*; D000099163:Myosin Binding Protein C
D002352:Carrier Proteins; D009218:Myosins; D000099163:Myosin Binding Protein C