title: Splice variant specific modulation of CaV1.2 calcium channel by galectin-1 regulates arterial constriction.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  Our hypothesis is that Gal-1 interacts directly with Ca(V)1.2 channel at the I-II loop to affect arterial constriction.
  
  
  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(V)1.2(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 I(Ca,L). The physiological significance of Gal-1 mediated splice variant-specific inhibition of Ca(V)1.2 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.
  
  
  CONCLUSIONS
  The above data indicated that Gal-1 regulates I(Ca,L) via decreasing the functional surface expression of Ca(V)1.2 channels in a splice variant selective manner and such a mechanism may play a role in modulating vascular constriction.
authors: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors: Juejin
authors: J
authors: Wang
authors: Sharon S C
authors: SS
authors: Thio
authors: Sophia S H
authors: SS
authors: Yang
authors: Dejie
authors: D
authors: Yu
authors: Chye Yun
authors: CY
authors: Yu
authors: Yuk Peng
authors: YP
authors: Wong
authors: Ping
authors: P
authors: Liao
authors: Shengnan
authors: S
authors: Li
authors: Tuck Wah
authors: TW
authors: Soong
mesh_terms: D000818:Animals; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D037483:Galectin 1 / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D015640:Ion Channel Gating; D009130:Muscle, Smooth / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012326:RNA Splicing; D051381:Rats; D020798:Two-Hybrid System Techniques; D014661:Vasoconstriction / Q000235:genetics / Q000502:physiology*
chemical_list: C079146:CACNA1C protein, human; C504728:Cacna1c protein, rat; D020746:Calcium Channels, L-Type; D037483:Galectin 1; C445499:LGALS1 protein, human; D020033:Protein Isoforms; D001464:Barium; D002118:Calcium