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Obscurin, a giant muscle protein of the immunoglobulin superfamily: developmental expression and role in myofibril assembly
Author(s) -
Borisov Andrei B,
Raeker Maide O,
Geisler Sarah B,
Russell Mark W
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a202-d
Subject(s) - obscurin , myogenesis , myofibril , titin , biology , nebulin , microbiology and biotechnology , gene isoform , downregulation and upregulation , myocyte , sarcomere , myosin , intercalated disc , intracellular , biochemistry , gene , gap junction
Obscurin is the third member of a family of giant muscle‐specific proteins that includes titin and nebulin. It is composed of multiple linked immunoglobulin domains, two fibronectin domains, Rho‐guanine nucleotide exchange factor, a calmodulin‐binding IQ motif and two kinase‐like domains. The goal of this study was to investigate the developmental expression of obscurin in cardiac and skeletal muscle during the process of differentiation in situ and in cell culture. We found that in murine striated muscle obscurin was clearly detected begining at day 10 post conception and that its expression was progressively upregulated during development. The localization changed from a diffuse pattern at early stages of myogenesis to concentration in the middle of A bands and, to a lesser extent, in Z‐disks of maturing myofibrils. This shows that developmental upregulation of obscurin in muscle cells is associated with differentiation of the contractile apparatus. Our experiments with selective downregulation of obscurin expression show that this protein is responsible for structural integration of myofibrils, their lateral alignment into a register at Z‐discs and M‐lines and for structural coupling of the contractile apparatus with the intracellular Ca2+‐transporting tubular network. Multiple isoforms of obscurin are generated by alternative splicing, and its individual isotypes have distinct expression patterns. The coordinated developmental expression of obscurin isoforms suggests that these novel proteins play vital and synergistic roles during myogenesis. Supported by the MDA and NIH HL075093.