Expression and functional characteristics of calpain 3 isoforms generated through tissue-specific transcriptional and posttranscriptional events

Détails

ID Serval
serval:BIB_8D224500E203
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Expression and functional characteristics of calpain 3 isoforms generated through tissue-specific transcriptional and posttranscriptional events
Périodique
Molecular and Cellular Biology
Auteur(s)
Herasse  M., Ono  Y., Fougerousse  F., Kimura  E., Stockholm  D., Beley  C., Montarras  D., Pinset  C., Sorimachi  H., Suzuki  K., Beckmann  J. S., Richard  I.
ISSN
0270-7306 (Print)
Statut éditorial
Publié
Date de publication
06/1999
Volume
19
Numéro
6
Pages
4047-55
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jun
Résumé
Calpain 3 is a nonlysosomal cysteine protease whose biological functions remain unknown. We previously demonstrated that this protease is altered in limb girdle muscular dystrophy type 2A patients. Preliminary observations suggested that its gene is subjected to alternative splicing. In this paper, we characterize transcriptional and posttranscriptional events leading to alterations involving the NS, IS1, and IS2 regions and/or the calcium binding domains of the mouse calpain 3 gene (capn3). These events can be divided into three groups: (i) splicing of exons that preserve the translation frame, (ii) inclusion of two distinct intronic sequences between exons 16 and 17 that disrupt the frame and would lead, if translated, to a truncated protein lacking domain IV, and (iii) use of an alternative first exon specific to lens tissue. In addition, expression of these isoforms seems to be regulated. Investigation of the proteolytic activities and titin binding abilities of the translation products of some of these isoforms clearly indicated that removal of these different protein segments affects differentially the biochemical properties examined. In particular, removal of exon 6 impaired the autolytic but not fodrinolytic activity and loss of exon 16 led to an increased titin binding and a loss of fodrinolytic activity. These results are likely to impact our understanding of the pathophysiology of calpainopathies and the development of therapeutic strategies.
Mots-clé
Alternative Splicing Animals Brain/metabolism Calpain/*genetics/*metabolism Carrier Proteins/metabolism Cells, Cultured Cloning, Molecular DNA Primers Embryo/anatomy & histology/metabolism Humans In Situ Hybridization Introns *Isoenzymes Lens, Crystalline/anatomy & histology/metabolism Mice Mice, Inbred BALB C Microfilament Proteins/metabolism Models, Genetic Muscle Proteins/metabolism Muscle, Skeletal/metabolism Muscle, Smooth/metabolism Myocardium/metabolism Peptide Fragments/metabolism Protein Kinases/metabolism *RNA Processing, Post-Transcriptional Rats Reverse Transcriptase Polymerase Chain Reaction Time Factors Tissue Distribution *Transcription, Genetic
Pubmed
Web of science
Création de la notice
25/01/2008 17:17
Dernière modification de la notice
03/03/2018 19:15
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