title: Complete primary structure of the I-band region of connectin at which mechanical property is modulated in zebrafish heart and skeletal muscle.
abstract: Connectin, also called titin, is the largest protein with a critical function as a molecular spring during contraction and relaxation of striated muscle; its mutation leads to severe myopathy and cardiomyopathy. To uncover the cause of this pathogenesis, zebrafish have recently been used as disease models because they are easier to genetically modify than mice. Although the gene structures and putative primary structures of zebrafish connectin have been determined, the actual primary structures of zebrafish connectin in heart and skeletal muscles remain unclear because of its large size and the PCR amplification-associated difficulties. In this research, using RT-PCR amplification from zebrafish heart and skeletal muscles, we determined the complete primary structures of zebrafish connectin in the I-band region at which mechanical property is modulated by alternative splicing. Our results showed that the domain structures of zebrafish connectins were largely similar to those of human connectins; however, the splicing pathways in the middle-Ig segment and the PEVK segment were highly diverse in every isoform. We also found that a set of 10 Ig domains in the middle-Ig segment of zebrafish connectin had been triplicated in human connectin. Because these triplicate regions are expressed in human leg and diaphragm, our findings may provide insight into the establishment of walking with limbs and lung respiration during tetrapod evolution.
authors.affiliation: First Department of Physiology, Kawasaki Medical School, Kurashiki 701-0192, Japan. Electronic address: hanashima@med.kawasaki-m.ac.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Hanashima
authors.affiliation: First Department of Physiology, Kawasaki Medical School, Kurashiki 701-0192, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Hashimoto
authors.affiliation: First Department of Physiology, Kawasaki Medical School, Kurashiki 701-0192, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ujihara
authors.affiliation: First Department of Physiology, Kawasaki Medical School, Kurashiki 701-0192, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Honda
authors.affiliation: First Department of Physiology, Kawasaki Medical School, Kurashiki 701-0192, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yobimoto
authors.affiliation: First Department of Physiology, Kawasaki Medical School, Kurashiki 701-0192, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Kodama
authors.affiliation: First Department of Physiology, Kawasaki Medical School, Kurashiki 701-0192, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mohri
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D064211:Connectin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D006801:Humans; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010802:Phylogeny; D000072417:Protein Domains; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D019154:Protein Splicing; D012518:Sarcomeres / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D064211:Connectin; D020033:Protein Isoforms; D029961:Zebrafish Proteins
keywords: Connectin; Heart; Molecular evolution; Muscle; Titin; Zebrafish