Assembly of the cardiac I-band region of titin/connectin: expression of the cardiac-specific regions and their structural relation to the elastic segments |
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Authors: | Mathias Gautel Eero Lehtonen Fricke Pietruschka |
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Affiliation: | (1) Biological Structures Division, European Molecular Biology Laboratory, Postfach 102209, 69012 Heidelberg, Germany;(2) Department of Pathology, University of Helsinki, Finland;(3) Max-Planck-Institut für molekulare Physiologie, Dortmund, Germany |
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Abstract: | Summary The giant molecule titin (also called connectin) provides an elastic connection in the I-band between the Z-disk and A-band of striated muscle. This region is assembled in a tissue-specific way by extensive differential splicing events. We have raised monoclonal antibodies against the two N2-line isoforms of titin and demonstrate that both forms of cardiac I-band titin are constitutively co-expressed in atrial and ventricular muscle. In developing mouse embryos, the expression of the cardiac N2-B isoform remains strictly cardiac-specific and is linked to the expression of the ubiquitous N2-A isoform. The mechanical function of the cardiac N2-line region was investigated ultrastructurally. Immunoelectron microscopy reveals that the N2-B region separates two mechanically distinct sections of titin with a hyperextensible segment spanning the distance to the Z-disk. The formation of a plateau in the extension of cardiac titin rules out that Ig-domains can be unfolded as a mechanism of elasticity. |
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