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|Title:||Splice variant specific modulation of CaV1.2 calcium channel by galectin-1 regulates arterial constriction|
vascular smooth muscle cell
|Source:||Wang, J., Thio, S.S.C., Yang, S.S.H., Yu, D., Yu, C.Y., Wong, Y.P., Liao, P., Li, S., Soong, T.W. (2011-11-11). Splice variant specific modulation of CaV1.2 calcium channel by galectin-1 regulates arterial constriction. Circulation Research 109 (11) : 1250-1258. ScholarBank@NUS Repository. https://doi.org/10.1161/CIRCRESAHA.111.248849|
|Abstract:||Rationale: Ca V1.2 channels are essential for excitation-contraction coupling in the cardiovascular system, and alternative splicing optimizes its role. Galectin-1 (Gal-1) has been reported to regulate vascular smooth muscle cell (VSMC) function and play a role in pulmonary hypertension. We have identified Gal-1 multiple times in yeast 2-hybrid assays using the Ca V1.2 I-II loop as bait. Objective: Our hypothesis is that Gal-1 interacts directly with Ca V1.2 channel at the I-II loop to affect arterial constriction. Methods and Results: Unexpectedly, Gal-1 was found to selectively bind to the I-II loop only in the absence of alternatively spliced exon 9*. We found that the current densities of Ca V1.2 Δ9* channels were significantly inhibited as a result of decreased functional surface expression due to the binding of Gal-1 at the export signal located on the C-terminus of exon 9. Moreover, the suppression of Gal-1 expression by siRNA in rat A7r5 and isolated VSMCs produced the opposite effect of increased ICa,L. The physiological significance of Gal-1 mediated splice variant-specific inhibition of Ca V1.2 channels was demonstrated in organ bath culture where rat MAs were reversibly permeabilized with Gal-1 siRNA and the arterial wall exhibited increased K +-induced constriction. Conclusion: The above data indicated that Gal-1 regulates ICa,L via decreasing the functional surface expression of Ca V1.2 channels in a splice variant selective manner and such a mechanism may play a role in modulating vascular constriction. © 2011 American Heart Association, Inc.|
|Source Title:||Circulation Research|
|Appears in Collections:||Staff Publications|
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