Developmental changes in rat cardiac titin/connectin: transitions in normal animals and in mutants with a delayed pattern of isoform transition
- 208 Downloads
Rat cardiac titin undergoes developmental changes in isoform expression during the period from late embryonic through the first 20–25 days of life. At least five size classes of titin isoforms have been identified using SDS agarose gel electrophoresis. The longest normal isoform is expressed in the embryonic stages, and it is progressively replaced with increasingly smaller versions. The isoform switching is consistent with changes in resting tension from lower values in one-day neonates to higher levels in adult myocytes. Considerable micro-heterogeneity in alternative splicing patterns also was found, particularly in the N2BA PEVK region of human, rat, and dog ventricle. A rat mutation has been identified in which the embryonic-neonatal titin isoform transitions are markedly delayed. These mutant animals may prove useful for examining the role of titin in stretch-activated signal transduction and in the Frank–Starling relationship.
KeywordsExon Expression Cardiac Titin PEVK Region PEVK Segment N2BA Isoforms
Unable to display preview. Download preview PDF.
This work was supported by the College of Agricultural and Life Sciences, University of Wisconsin-Madison and by grants from the National Institutes of Health (HL47053; HL62466; HL77196).
- Bang ML, Centner T, Fornoff F, Geach AJ, Gotthardt M, McNabb M, Witt CC, Labeit D, Gregorio CC, Granzier H, Labeit S (2001) The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system. Circ Res 89:1065–1072PubMedGoogle Scholar
- Freiburg A, Trombitas K, Hell W, Cazorla O, Fougerousse F, Centner T, Kolmerer B, Witt C, Beckmann JS, Gregorio CC, Granzier H, Labeit S (2000) Series of exon-skipping events in the elastic spring region of titin as the structural basis for myofibrillar elastic diversity. Circ Res 86:1114–1121PubMedGoogle Scholar
- Furst DO, Osborn M, Nave R, Weber K (1988) The organization of the titin filaments in the half-sarcomere revealed by monoclonal antibodies in immunoelectron microscopy: a map of ten nonrepetitive epitopes starting at the Z-line extends close to the M-line. J Cell Biol 106:1563–1572CrossRefPubMedGoogle Scholar
- Maruyama K (1976) Connectin, an elastic protein from myofibrils. J Biochem (Tokyo) 80:405–407Google Scholar