title: Obscurin is required for the lateral alignment of striated myofibrils in zebrafish.
abstract: Obscurin/obscurin-MLCK is a giant sarcomere-associated protein with multiple isoforms whose interactions with titin and small ankyrin-1 suggest that it has an important role in myofibril assembly, structural support, and the sarcomeric alignment of the sarcoplasmic reticulum. In this study, we characterized the zebrafish orthologue of obscurin and examined its role in striated myofibril assembly. Zebrafish obscurin was expressed in the somites and central nervous system by 24 hours post-fertilization (hpf) and in the heart by 48 hpf. Depletion of obscurin using two independent morpholino antisense oligonucleotides resulted in diminished numbers and marked disarray of skeletal myofibrils, impaired lateral alignment of adjacent myofibrils, disorganization of the sarcoplasmic reticulum, somite segmentation defects, and abnormalities of cardiac structure and function. This is the first demonstration that obscurin is required for vertebrate cardiac and skeletal muscle development. The diminished capacity to generate and organize new myofibrils in response to obscurin depletion suggests that it may have a vital role in the causation of or adaptation to cardiac and skeletal myopathies.
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Maide O
authors.initials: MO
authors.lastname: Raeker
authors.forename: Fengyun
authors.initials: F
authors.lastname: Su
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Geisler
authors.forename: Andrei B
authors.initials: AB
authors.lastname: Borisov
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Kontrogianni-Konstantopoulos
authors.forename: Susan E
authors.initials: SE
authors.lastname: Lyons
authors.forename: Mark W
authors.initials: MW
authors.lastname: Russell
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning; D017124:Conserved Sequence; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006321:Heart / Q000196:embryology; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D009210:Myofibrils / Q000378:metabolism* / Q000648:ultrastructure; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D010802:Phylogeny; D016415:Sequence Alignment; D019170:Somites / Q000378:metabolism / Q000648:ultrastructure; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D009124:Muscle Proteins; D029961:Zebrafish Proteins; C513831:obscna protein, zebrafish; D009219:Myosin-Light-Chain Kinase