title: Assembly of the cardiac I-band region of titin/connectin: expression of the cardiac-specific regions and their structural relation to the elastic segments.
abstract: 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.
authors.affiliation: European Molecular Biology Laboratory, Biological Structures Division, Heidelberg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Gautel
authors.forename: E
authors.initials: E
authors.lastname: Lehtonen
authors.forename: F
authors.initials: F
authors.lastname: Pietruschka
mesh_terms: D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D064211:Connectin; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D016253:Microscopy, Immunoelectron; D009124:Muscle Proteins / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011494:Protein Kinases / Q000378:metabolism*; D012518:Sarcomeres / Q000378:metabolism
chemical_list: D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D064211:Connectin; D008565:Membrane Proteins; D009124:Muscle Proteins; C577285:TTN protein, human; D011494:Protein Kinases