Titin as a Chromosomal Protein
We identified titin as a chromosomal protein using a human autoimmune scleroderma serum. We cloned the corresponding gene in the fruitfly, Droso-phila melanogaster. We have demonstrated that titin is not only expressed and localized in striated muscle but is also distributed uniformly on condensed mitotic chromosomes using multiple antibodies directed against different domains of both Drosophila and vertebrate titin. Titin is a giant sarcomeric protein responsible for the elasticity of striated muscle. Titin may also function as a molecular scaffold during myofibril assembly. We hypothesize that titin is a component of chromosomes that may function to determine chromosome structure and provide elasticity, playing a role similar to that proposed for titin in muscle. We have identified mutations in Drosophila Titin (D-Titin) and are characterizing phenotypes in muscle and chromosomes.
KeywordsMitotic Chromosome Chromosome Condensation Chromosomal Protein Limb Girdle Muscular Dystrophy Familial Hypertrophic Cardiomyopathy
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- Fritzler MJ. Autoantibodies: diagnostic fingerprints and etiological perplexities. Clin Invest Med 1997;20:103–115.Google Scholar
- Itoh Y, Suzuki T, Kimura S, Ohashi K, Higuchi H, Sawada H, Shimizu T, Shibata M, Maruyama K. Extensible and less-extensible domains of connectin filaments in stretched vertebrate skeletal muscle as detected by immunofluorescence and immunoelectron microscopy using monoclonal antibodies. J Biochem 1988;104:504–508.PubMedGoogle Scholar
- Machado C. Isolating the D-Titin gene in Drosophila melanogasterusing a human autoimmune serum. PhD. Thesis, University of Porto, 1998.Google Scholar
- Mole-Bajer J, Bajer AS, Zinkowski RP, Balczon RD, Brinkley BR. Autoantibodies from a patient with scleroderma CREST recognized kinetochores of the higher plant Haemanthus. Proc NatlAcadSci USA 1990;17:1627–1631.Google Scholar
- Obermann WM, Gautel M, Steiner F, van der Ven PF, Weber K, Fürst DO. The structure of the sarcomeric M band: localization of defined domains of myomesin, M-protein, and the 250 kD carboxy-terminal region of titin by immunoelectron microscopy. J Cell Biol 1996;134:1441–1453.CrossRefPubMedGoogle Scholar
- Saunders WS, Chue C, Goebl M, Craig C, Clark RF, Powers JA, Eissenberg JC, Elgin SC, Rothfield NF, Earnshaw WC. Molecular cloning of a human homologue of Drosophila heterochromatin protein HP1 using anti-centromere autoantibodies with anti-chromo specificity. J Cell Sci 1993;104:573–582.PubMedGoogle Scholar
- Sebastyén MG, Wolff JA, Greaser ML. Characterization of a 5.4 kb cDNA fragment from the Z-line of rabbit cardiac titin reveals phosphorylation sites for proline-directed kinases. J Cell Sci 1995;108:3029–3037.Google Scholar
- Sorimachi H, Kinbara K, Kimura S, Takahashi M, Ishiura S, Sasagawa N, Sorimachi N, Shimada H, Tagawa K, Maruyama K, Suzuki K. Muscle-specific calpain, p94, responsible for limb girdle muscular dystrophy type 2A, associates with connectin through IS2, a p94-specific sequence. J Mol Biochem 1995;270:31158–31162.Google Scholar
- Tan EM, Reimer G, Sullivan K. Iniracellular autoantigens: diagnostic fingerprints but aetiological dilemmas.Chichester, John Wiley & Sons, 1987.Google Scholar
- Wolffe AP. Chromatin: structure and function. San Diego, CA: Academic Press, 1998.Google Scholar