Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep35247
Title: Aberrant Splicing Promotes Proteasomal Degradation of L-type Ca v 1.2 Calcium Channels by Competitive Binding for CaV β Subunits in Cardiac Hypertrophy
Authors: Hu, Z 
Wang, J.-W 
Yu, D 
Soon, J.L 
De Kleijn, D.P.V 
Foo, R 
Liao, P 
Colecraft, H.M
Soong, T.W 
Keywords: calcium channel L type
L-type calcium channel alpha(1C)
proteasome
alternative RNA splicing
animal
binding competition
cardiomegaly
genetics
metabolism
protein degradation
rat
RNA splicing
Alternative Splicing
Animals
Binding, Competitive
Calcium Channels, L-Type
Cardiomegaly
Proteasome Endopeptidase Complex
Proteolysis
Rats
RNA Splicing
Issue Date: 2016
Citation: Hu, 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
Abstract: Decreased 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).
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/173985
ISSN: 20452322
DOI: 10.1038/srep35247
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