Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep35247
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dc.titleAberrant Splicing Promotes Proteasomal Degradation of L-type Ca v 1.2 Calcium Channels by Competitive Binding for CaV β Subunits in Cardiac Hypertrophy
dc.contributor.authorHu, Z
dc.contributor.authorWang, J.-W
dc.contributor.authorYu, D
dc.contributor.authorSoon, J.L
dc.contributor.authorDe Kleijn, D.P.V
dc.contributor.authorFoo, R
dc.contributor.authorLiao, P
dc.contributor.authorColecraft, H.M
dc.contributor.authorSoong, T.W
dc.date.accessioned2020-09-02T06:47:41Z
dc.date.available2020-09-02T06:47:41Z
dc.date.issued2016
dc.identifier.citationHu, Z, Wang, J.-W, Yu, D, Soon, J.L, De Kleijn, D.P.V, Foo, R, Liao, P, Colecraft, H.M, Soong, T.W (2016). Aberrant Splicing Promotes Proteasomal Degradation of L-type Ca v 1.2 Calcium Channels by Competitive Binding for CaV β Subunits in Cardiac Hypertrophy. Scientific Reports 6 : 35247. ScholarBank@NUS Repository. https://doi.org/10.1038/srep35247
dc.identifier.issn20452322
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/173985
dc.description.abstractDecreased expression and activity of Ca V1.2 calcium channels has been reported in pressure overload-induced cardiac hypertrophy and heart failure. However, the underlying mechanisms remain unknown. Here we identified in rodents a splice variant of Ca V1.2 channel, named Ca V1.2 e21+22, that contained the pair of mutually exclusive exons 21 and 22. This variant was highly expressed in neonatal hearts. The abundance of this variant was gradually increased by 12.5-folds within 14 days of transverse aortic banding that induced cardiac hypertrophy in adult mouse hearts and was also elevated in left ventricles from patients with dilated cardiomyopathy. Although this variant did not conduct Ca 2+ ions, it reduced the cell-surface expression of wild-type Ca V1.2 channels and consequently decreased the whole-cell Ca 2+ influx via the Ca V1.2 channels. In addition, the Ca V1.2 e21+22 variant interacted with Ca V? subunits significantly more than wild-type Ca V1.2 channels, and competition of Ca V? subunits by Ca V1.2 e21+22 consequently enhanced ubiquitination and subsequent proteasomal degradation of the wild-type Ca V1.2 channels. Our findings show that the resurgence of a specific neonatal splice variant of Ca V1.2 channels in adult heart under stress may contribute to heart failure. © 2016 The Author(s).
dc.sourceUnpaywall 20200831
dc.subjectcalcium channel L type
dc.subjectL-type calcium channel alpha(1C)
dc.subjectproteasome
dc.subjectalternative RNA splicing
dc.subjectanimal
dc.subjectbinding competition
dc.subjectcardiomegaly
dc.subjectgenetics
dc.subjectmetabolism
dc.subjectprotein degradation
dc.subjectrat
dc.subjectRNA splicing
dc.subjectAlternative Splicing
dc.subjectAnimals
dc.subjectBinding, Competitive
dc.subjectCalcium Channels, L-Type
dc.subjectCardiomegaly
dc.subjectProteasome Endopeptidase Complex
dc.subjectProteolysis
dc.subjectRats
dc.subjectRNA Splicing
dc.typeArticle
dc.contributor.departmentDEPT OF PHYSIOLOGY
dc.contributor.departmentDEPT OF SURGERY
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.contributor.departmentDEPT OF MEDICINE
dc.description.doi10.1038/srep35247
dc.description.sourcetitleScientific Reports
dc.description.volume6
dc.description.page35247
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