Effect of bestrophin-1 on L-type Ca2+ channel activity depends on the Ca2+ channel beta-subunit

Reichhart, Nadine; Milenkovic, Vladimir M.; Halsband, Claire-Amelie; Cordeiro, Sönke; Strauß, Olaf

doi:10.1016/j.exer.2010.08.001

Cited by 41 publications

(59 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, bestrophin-1 influences intracellular Ca 2 + signaling in the RPE. On one hand bestrophin-1 interacts with L-type Ca 2+ channels of the Ca V 1.3 subtype regulating their surface expression and conductance (Rosenthal et al 2006;Yu et al 2008;Reichhart et al 2010;Milenkovic et al 2011b). On the other hand bestrophin-1 acts as an intracellular Cl channel which helps to accumulate into or to release Ca 2+ from cytosolic Ca 2+ stores by conducting Cl as negatively charged counter-ion for the transmembranal transport of the positively charged Ca 2+ ions (Gomez et al 2013).…”

Section: +mentioning

confidence: 99%

Contribution of Ion Channels in Calcium Signaling Regulating Phagocytosis: MaxiK, Cav1.3 and Bestrophin-1

Strauß

Reichhart

Gómez

et al. 2015

Retinal Degenerative Diseases

Self Cite

View full text Add to dashboard Cite

Mutations in the BEST1 gene lead to a variety of retinal degenerations including Best's vitelliforme macular degeneration. The BEST1 gene product, bestrophin-1, is expressed in the retinal pigment epithelium (RPE). It is likely that mutant bestrophin-1 impairs functions of the RPE which support photoreceptor function and will thus lead to retinal degeneration. However, the RPE function which is influenced by bestrophin-1 is so far not identified. Previously we showed that bestrophin-1 interacts with L-type Ca²⁺ channels of the CaV1.3 subtype and that the endogenously expressed bestrophin-1 is required for intracellular Ca²⁺ regulation. A hallmark of Best's disease is the fast lipofuscin accumulation occurring already at young ages. Therefore, we addressed the hypothesis that bestrophin-1 might influence phagocytosis of photoreceptor outer segments (POS) by the RPE. Here, siRNA knock-down of bestrophin-1 expression as well as inhibition of L-type Ca²⁺ channel activity modulated the POS phagocytosis in vitro. In vivo CaV1.3 expression appeared to be diurnal regulated with a higher expression rate in the afternoon. Compared to wild-type littermates, Ca V 1.3 (-/-) mice showed a shift in the circadian POS phagocytosis with an increased activity in the afternoon. Thus we suggest that mutant bestrophin-1 leads to an impaired regulation of the POS phagocytosis by the RPE which would explain the fast lipofuscin accumulation in Best patients.

show abstract

Section: +mentioning

confidence: 99%

Contribution of Ion Channels in Calcium Signaling Regulating Phagocytosis: MaxiK, Cav1.3 and Bestrophin-1

Strauß

Reichhart

Gómez

et al. 2015

Retinal Degenerative Diseases

Self Cite

View full text Add to dashboard Cite

show abstract

“…This carboxyl terminal region may hold the key to understanding the pathogenesis of ARB, and future studies should investigate why and how the loss of this region may lead to retinal dysfunction. Since the C-terminus has been shown to play roles in the regulation and interaction of voltage dependent Ca 2þ channels, 25,42,45,46 the Best1 I366fsX18 mutant may impair Ca 2þ homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Autosomal Recessive Bestrophinopathy Is Not Associated With the Loss of Bestrophin-1 Anion Channel Function in a Patient With a NovelBEST1Mutation

Johnson

Bachman

Gilles

et al. 2015

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Citation: Johnson AA, Bachman LA, Gilles BJ, et al. Autosomal recessive bestrophinopathy is not associated with the loss of bestrophin-1 anion channel function in a patient with a novel BEST1 mutation. Invest Ophthalmol Vis Sci. 2015;56:4619-4630. DOI:10.1167/iovs.15-16910 PURPOSE. Mutations in BEST1, encoding bestrophin-1 (Best1), cause autosomal recessive bestrophinopathy (ARB). Encoding bestrophin-1 is a pentameric anion channel localized to the basolateral plasma membrane of the RPE. Here, we characterize the effects of the mutations R141H (CGC > CAC) and I366fsX18 (c.1098_1100þ7del), identified in a patient in our practice, on Best1 trafficking, oligomerization, and channel activity. METHODS. Currents of ClÀ were assessed in transfected HEK293 cells using whole-cell patch clamp. Best1 localization was assessed by confocal microscopy in differentiated, humaninduced pluripotent stem cell-derived RPE (iPSC-RPE) cells following expression of mutants via adenovirus-mediated gene transfer. Oligomerization was evaluated by coimmunoprecipitation in iPSC-RPE and MDCK cells. À currents, this indicates that ARB in this patient is not caused by a loss of channel activity. Moreover, Best1 I366fsX18 differs from Best1 in that it lacks most of the cytosolic C-terminal domain, suggesting that the loss of this region contributes significantly to the pathogenesis of ARB in this patient. RESULTS. Compared to

show abstract

“…Bestrophin1 (Best1) is an ER-localized, Ca 2+ -activated Cl À channel that interacts with STIM1 and may form the counterion channel that accompanies Ca 2+ movement in and out of the store (Barro-Soria et al 2010). Although it is unknown whether Best1 translocates in association with STIM1 into punctae at the plasma membrane, Best1 can inhibit Ca V 1.3 channels through association with the β4 subunit (Yu et al 2008;Reichhart et al 2010). Although not proven in β-cells, these inhibitory effects of STIM1 and Best1 on Ca V 1.2 and Ca V 1.3 might be important for the regulation of glucose-induced insulin secretion (see text).…”

Section: Stromal Interaction Molecule (Stim)mentioning

confidence: 99%

β Cell Store-Operated Ion Channels

Leech

Kopp

Philipson

et al. 2014

Islets of Langerhans

View full text Add to dashboard Cite

Effect of bestrophin-1 on L-type Ca2+ channel activity depends on the Ca2+ channel beta-subunit

Cited by 41 publications

References 18 publications

Contribution of Ion Channels in Calcium Signaling Regulating Phagocytosis: MaxiK, Cav1.3 and Bestrophin-1

Contribution of Ion Channels in Calcium Signaling Regulating Phagocytosis: MaxiK, Cav1.3 and Bestrophin-1

Autosomal Recessive Bestrophinopathy Is Not Associated With the Loss of Bestrophin-1 Anion Channel Function in a Patient With a NovelBEST1Mutation

β Cell Store-Operated Ion Channels

Contact Info

Product

Resources

About