Obscurin Interacts with a Novel Isoform of MyBP-C Slow at the Periphery of the Sarcomeric M-Band and Regulates Thick Filament Assembly
- 15 June 2009
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 20 (12), 2963-2978
- https://doi.org/10.1091/mbc.e08-12-1251
Abstract
Obscurin is a multidomain protein composed of adhesion and signaling domains that plays key roles in the organization of contractile and membrane structures in striated muscles. Overexpression of the second immunoglobulin domain of obscurin (Ig2) in developing myotubes inhibits the assembly of A- and M-bands, but not Z-disks or I-bands. This effect is mediated by the direct interaction of the Ig2 domain of obscurin with a novel isoform of myosin binding protein-C slow (MyBP-C slow), corresponding to variant-1. Variant-1 contains all the structural motifs present in the known forms of MyBP-C slow, but it has a unique COOH terminus. Quantitative reverse transcription-polymerase chain reaction indicated that MyBP-C slow variant-1 is expressed in skeletal muscles both during development and at maturity. Immunolabeling of skeletal myofibers with antibodies to the unique COOH terminus of variant-1 demonstrated that, unlike other forms of MyBP-C slow that reside in the C-zones of A-bands, variant-1 preferentially concentrates around M-bands, where it codistributes with obscurin. Overexpression of the Ig2 domain of obscurin or reduction of expression of obscurin inhibited the integration of variant-1 into forming M-bands in skeletal myotubes. Collectively, our experiments identify a new ligand of obscurin at the M-band, MyBP-C slow variant-1 and suggest that their interaction contributes to the assembly of M- and A-bands.Keywords
This publication has 59 references indexed in Scilit:
- Obscurin Targets Ankyrin-B and Protein Phosphatase 2A to the Cardiac M-linePublished by Elsevier BV ,2008
- The Rho-Guanine Nucleotide Exchange Factor Domain of Obscurin Regulates Assembly of Titin at the Z-Disk through Interactions with Ran Binding Protein 9Molecular Biology of the Cell, 2008
- Interactions with titin and myomesin target obscurin and obscurin-like 1 to the M-band – implications for hereditary myopathiesJournal of Cell Science, 2008
- Early incorporation of obscurin into nascent sarcomeres: implication for myofibril assembly during cardiac myogenesisHistochemistry and Cell Biology, 2008
- Mapping the Binding Site on Small Ankyrin 1 for ObscurinPublished by Elsevier BV ,2007
- Different obscurin isoforms localize to distinct sites at sarcomeresFEBS Letters, 2007
- Molecular interactions with obscurin are involved in the localization of muscle-specific small ankyrin1 isoforms to subcompartments of the sarcoplasmic reticulumExperimental Cell Research, 2006
- De novo myofibrillogenesis in C2C12cells: evidence for the independent assembly of M bands and Z disksAmerican Journal of Physiology-Cell Physiology, 2006
- Obscurin regulates the organization of myosin into A bandsAmerican Journal of Physiology-Cell Physiology, 2004
- Complete primary structure of chicken cardiac C-protein (MyBP-C) and its expression in developing striated musclesJournal of Molecular and Cellular Cardiology, 1995