ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
The best disease-linked Cl- channel hBest1 regulates Ca V 1 (L-type) Ca2+ channels via src-homology-binding domains.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 86 citations in OpenAlex.
- CaActa physiologica (Oxford, England) · 2026Review
- Review of the clinical electrooculogram - Part 1: Mechanism of the Light-Rise.Documenta ophthalmologica. Advances in ophthalmology · 2026Review
- Molecular Partners of Voltage-Gated Calcium Channel β and αThe Journal of membrane biology · 2026Review
- GABA Release from Astrocytes in Health and Disease.International journal of molecular sciences · 2022Review
- Structure and Function of the Bestrophin family of calcium-activated chloride channels.Channels (Austin, Tex.) · 2021Review
- Evaluating BEST1 mutations in pluripotent stem cell-derived retinal pigment epithelial cells.Methods in enzymology · 2021Article
- Article
- Bestrophin 1 and retinal disease.Progress in retinal and eye research · 2017Review
- Characterization of the effects of Cl⁻ channel modulators on TMEM16A and bestrophin-1 Ca²⁺ activated Cl⁻ channels.Pflugers Archiv : European journal of physiology · 2015Article
- Autosomal Recessive Bestrophinopathy Is Not Associated With the Loss of Bestrophin-1 Anion Channel Function in a Patient With a Novel BEST1 Mutation.Investigative ophthalmology & visual science · 2015Article
- Bestrophin-1 influences transepithelial electrical properties and Ca2+ signaling in human retinal pigment epithelium.Molecular vision · 2015Article
- TMEM16A knockdown abrogates two different Ca(2+)-activated Cl (-) currents and contractility of smooth muscle in rat mesenteric small arteries.Pflugers Archiv : European journal of physiology · 2014Article
- The Cavβ1a subunit regulates gene expression and suppresses myogenin in muscle progenitor cells.The Journal of cell biology · 2014Article
- Disease-causing mutations associated with four bestrophinopathies exhibit disparate effects on the localization, but not the oligomerization, of Bestrophin-1.Experimental eye research · 2014Article
- Effects of alternative splicing on the function of bestrophin-1 calcium-activated chloride channels.The Biochemical journal · 2014Article
- Differential effects of Best disease causing missense mutations on bestrophin-1 trafficking.Human molecular genetics · 2013Article
- Role of bestrophin-1 in store-operated calcium entry in retinal pigment epithelium.Pflugers Archiv : European journal of physiology · 2013Article
- Three-dimensional distribution of the vitelliform lesion, photoreceptors, and retinal pigment epithelium in the macula of patients with best vitelliform macular dystrophy.Archives of ophthalmology (Chicago, Ill. : 1960) · 2012Article
- Anion-sensitive fluorophore identifies the Drosophila swell-activated chloride channel in a genome-wide RNA interference screen.PloS one · 2012Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in the bestrophin-1 (Best1) gene are linked to several kinds of macular degeneration in both humans and dogs. Although bestrophins have been shown clearly to be Cl(-) ion channels, it is controversial whether Cl(-) channel dysfunction can explain the diseases. It has been suggested that bestrophins are multifunctional proteins: they may regulate voltage-gated Ca(2+) channels in addition to functioning as Cl(-) channels. Here, we show that human Best1 gene (hBest1) differentially modulates Ca(V)1.3 (L-type) voltage-gated Ca(2+) channels through association with the Ca(V)beta subunit. In transfected human embryonic kidney 293 cells, hBest1 inhibited Ca(V)1.3. Inhibition of Ca(V)1.3 was not observed in the absence of the beta subunit. Also, the hBest1 C terminus binds to Ca(V)beta subunits, suggesting that the effect of hBest1 was mediated by the Ca(V)beta subunit. The region of hBest1 responsible for the effect was localized to a region (amino acids 330-370) in the cytoplasmic C terminus that contains a predicted src-homology-binding domain that is not present in other bestrophin subtypes. Mutation of Pro(330) and Pro(334) abolished the effects of hBest1 on Ca(V)1.3. The effect was specific to hBest1; it was not observed with mouse Best1 (mBest1), mBest2, or mBest3. Wild-type hBest1 and the disease-causing mutants R92S, G299R, and D312N inhibited Ca(V) currents the same amount, whereas the A146K and G222E mutants were less effective. We propose that hBest1 regulates Ca(V) channels by interacting with the Ca(V)beta subunit and altering channel availability. Our findings reveal a novel function of bestrophin in regulation of Ca(V) channels and suggest a possible mechanism for the role of hBest1 in macular degeneration.
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