Linked Life Data

12459180

Source:http://linkedlifedata.com/resource/pubmed/id/12459180

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2002-12-2
pubmed:abstractText
Arrhythmogenic right ventricular dysplasia/cardiomyopathy type 2 (ARVD2, OMIM 600996) and stress-induced polymorphic ventricular tachycardia (VTSIP, OMIM 604772) are two cardiac diseases causing juvenile sudden death, both associated with mutations in the RyR2 calcium channel. By using a quantitative yeast two-hybrid system, we show that VTSIP- and ARVD2-associated point mutations influence positively and negatively, respectively, the binding of RyR2 to its gating protein FKBP12.6. These findings suggest that ARVD2 mutations increase RyR2-mediated calcium release to cytoplasm, while VTSIP mutations do not affect significantly cytosolic calcium levels, thereby explaining the clinical differences between the two diseases. The present two-hybrid system appears to be an efficient molecular tool to assay the binding of FKBP12s proteins to both cardiac RyR2 and skeletal muscle RyR1 isoforms, circumventing the full-length expression of this class of giant channels. We also provide evidence of the suitability of this system to test new drugs that target RyRs-FKBP12s interactions and do not affect yeast growth.
pubmed:language
eng
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:author
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
594-8
pubmed:dateRevised
2006-11-15
pubmed:articleTitle
The binding of the RyR2 calcium channel to its gating protein FKBP12.6 is oppositely affected by ARVD2 and VTSIP mutations.
pubmed:affiliation
Department of Biology, University of Padova, via U. Bassi 58/B, I-35131 Padua, Italy. natascia@telethon.bio.unipd.it