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

Détails

ID Serval
serval:BIB_38AC243700D0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Series of exon-skipping events in the elastic spring region of titin as the structural basis for myofibrillar elastic diversity
Périodique
Circulation Research
Auteur(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)
Statut éditorial
Publié
Date de publication
06/2000
Volume
86
Numéro
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
Résumé
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.
Mots-clé
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
Création de la notice
25/01/2008 17:18
Dernière modification de la notice
20/08/2019 14:28
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