Cellular Biology Splice Variant Specific Modulation of CaV1.2 Calcium Channel by Galectin-1 Regulates Arterial Constriction

نویسندگان

  • Juejin Wang
  • Sharon S.C. Thio
  • Sophia S.H. Yang
  • Dejie Yu
  • Chye Yun Yu
  • Yuk Peng Wong
  • Ping Liao
  • Shengnan Li
  • Tuck Wah Soong
چکیده

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Splice variant specific modulation of CaV1.2 calcium channel by galectin-1 regulates arterial constriction.

RATIONALE Ca(V)1.2 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(V)1.2 I-II loop as bait. OBJ...

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Alternative Splicing of L-type CaV1.2 Calcium Channels: Implications in Cardiovascular Diseases

L-type Cav1.2 calcium channels are the major pathway for Ca2+ influx to initiate the contraction of smooth and cardiac muscles. Alteration of Cav1.2 channel function has been implicated in multiple cardiovascular diseases, such as hypertension and cardiac hypertrophy. Alternative splicing is a post-transcriptional mechanism that expands Cav1.2 channel structures to modify function, pharmacologi...

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UNLABELLED Clevidipine, a dihydropyridine (DHP) analogue, lowers blood pressure (BP) by inhibiting l-type calcium channels (CaV1.2; gene CACNA1C) predominantly located in vascular smooth muscle (VSM). However, clinical observations suggest that clevidipine acts by a more complex mechanism. Clevidipine more potently reduces pulmonary vascular resistance (PVR) than systemic vascular resistance an...

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Aberrant Splicing Promotes Proteasomal Degradation of L-type CaV1.2 Calcium Channels by Competitive Binding for CaVβ Subunits in Cardiac Hypertrophy

Decreased expression and activity of CaV1.2 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 CaV1.2 channel, named CaV1.2e21+22, that contained the pair of mutually exclusive exons 21 and 22. This variant was highly expressed in neonatal hear...

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Mechanism of Cav1.2 channel modulation by the amino terminus of cardiac 2-subunits

L-type calcium channels are composed of a pore, 1c (CaV1.2), and accessory and 2 subunits. The -subunit core structure was recently resolved at high resolution, providing important information on many functional aspects of channel modulation. In this study we reveal differential novel effects of five 2-subunits isoforms expressed in human heart ( 2a-e) on the single L-type calcium channel curre...

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تاریخ انتشار 2011