Series of exon-skipping events in the elastic spring region of titin as the structural basis for myofibrillar elastic diversity

Details

Serval ID
serval:BIB_38AC243700D0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Series of exon-skipping events in the elastic spring region of titin as the structural basis for myofibrillar elastic diversity
Journal
Circulation Research
Author(s)
Freiburg  A., Trombitas  K., Hell  W., Cazorla  O., Fougerousse  F., Centner  T., Kolmerer  B., Witt  C., Beckmann  J. S., Gregorio  C. C., Granzier  H., Labeit  S.
ISSN
1524-4571 (Electronic)
Publication state
Published
Issued date
06/2000
Volume
86
Number
11
Pages
1114-21
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jun 9
Abstract
Titins are megadalton-sized filamentous polypeptides of vertebrate striated muscle. The I-band region of titin underlies the myofibrillar passive tension response to stretch. Here, we show how titins with highly diverse I-band structures and elastic properties are expressed from a single gene. The differentially expressed tandem-Ig, PEVK, and N2B spring elements of titin are coded by 158 exons, which are contained within a 106-kb genomic segment and are all subject to tissue-specific skipping events. In ventricular heart muscle, exons 101 kb apart are joined, leading to the exclusion of 155 exons and the expression of a 2.97-MDa cardiac titin N2B isoform. The atria of mammalian hearts also express larger titins by the exclusion of 90 to 100 exons (cardiac N2BA titin with 3.3 MDa). In the soleus and psoas skeletal muscles, different exon-skipping pathways produce titin transcripts that code for 3.7- and 3.35-MDa titin isoforms, respectively. Mechanical and structural studies indicate that the exon-skipping pathways modulate the fractional extensions of the tandem Ig and PEVK segments, thereby influencing myofibrillar elasticity. Within the mammalian heart, expression of different levels of N2B and N2BA titins likely contributes to the elastic diversity of atrial and ventricular myofibrils.
Keywords
Amino Acid Sequence/genetics Animals Base Sequence/genetics Elasticity Exons/*genetics Genome Humans Molecular Sequence Data Muscle Proteins/*genetics/metabolism/*physiology Muscle, Skeletal/metabolism Myocardium/metabolism Myofibrils/*physiology Protein Isoforms/genetics/metabolism/physiology Protein Kinases/*genetics/metabolism/*physiology Rabbits Rats Swine Transcription, Genetic
Pubmed
Web of science
Create date
25/01/2008 16:18
Last modification date
20/08/2019 13:28
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