ArticleThe Journal of physiology2009
Dysregulation of human bestrophin-1 by ceramide-induced dephosphorylation.
Article in The Journal of physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
15 citing papers in PubMed, 29 citations in OpenAlex.
- CaActa physiologica (Oxford, England) · 2026Review
- 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
- A clearer image of the structure and regulation of bestrophin.The Journal of general physiology · 2018Article
- An allosteric mechanism of inactivation in the calcium-dependent chloride channel BEST1.The Journal of general physiology · 2018Article
- Bestrophin 1 and retinal disease.Progress in retinal and eye research · 2017Review
- Article
- Disease-causing mutations associated with four bestrophinopathies exhibit disparate effects on the localization, but not the oligomerization, of Bestrophin-1.Experimental eye research · 2014Article
- Disease-causing mutations in BEST1 gene are associated with altered sorting of bestrophin-1 protein.International journal of molecular sciences · 2013Article
- Drosophila bestrophin-1 currents are regulated by phosphorylation via a CaMKII dependent mechanism.PloS one · 2013Article
- Ceramide signaling in retinal degeneration.Advances in experimental medicine and biology · 2012Review
- Characterization of the oligomeric structure of the Ca(2+)-activated Cl- channel Ano1/TMEM16A.The Journal of biological chemistry · 2011Article
- Bestrophins and retinopathies.Pflugers Archiv : European journal of physiology · 2010Review
- Regulating survival and development in the retina: key roles for simple sphingolipids.Journal of lipid research · 2010Review
- Beyond the cherry-red spot: Ocular manifestations of sphingolipid-mediated neurodegenerative and inflammatory disorders.Survey of ophthalmologyReview
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Best vitelliform macular dystrophy is an inherited autosomal dominant, juvenile onset form of macular degeneration caused by mutations in a chloride ion channel, human bestrophin-1 (hBest1). Mutations in Best1 have also been linked to several other forms of retinopathy. In addition to mutations, hBest1 dysfunction might come about by disruption of other processes that regulate Best1 function. Here we show that hBest1 chloride channel activity is regulated by ceramide and phosphorylation. We have identified a protein kinase C (PKC) phosphorylation site (serine 358) in hBest1 that is important for sustained channel function. Channel activity is maintained by PKC activators, protein phosphatase inhibitors, or pseudo-phosphorylation by substitution of glutamic acid for serine 358. When ceramide levels are elevated by exogenous addition of ceramide to the bath, by addition of bacterial sphingomyelinase, or by hypertonic stress, S358 is rapidly dephosphorylated. The dephosphorylation is mediated by protein phosphatase 2A. Hypertonic stress-induced dephosphorylation is blocked by a dihydroceramide, an inactive form of ceramide, and manumycin, an inhibitor of neutral sphingomyelinase. Our results support a model in which ceramide accumulation during early stages of retinopathy inhibits hBest1 function, leading to abnormal fluid transport across the retina, and enhanced inflammation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.