anti-Bestrophin 1 (BEST1) Antibodies

Fruit Fly (Drosophila melanogaster) Bestrophin 1 (BEST1) interaction partners

1. Bestrophin 1 (dBest1) as the Drosophila Cl(swell) channel

2. Using heterologous expression, we show here that human, Drosophila, and C. elegans bestrophins form oligomeric chloride channels, and that human bestrophin is sensitive to intracellular calcium

3. Here it is reported that bestrophin1 is a component of native Calcium channel at the plasma membrane.

4. bestrophin-1 chloride current is dually regulated by calcium and cell volume

Human Bestrophin 1 (BEST1) interaction partners

1. Study identified five novel mutations in BEST1 in four unrelated Indian families with autosomal recessive bestrophinopathy and autosomal dominant Best vitelliform macular dystrophy.

2. These data suggest that impaired phagocytosis is a trait common to the bestrophinopathies. Furthermore, ARB is not universally the result of NMD and ARB, in this patient, is not due to the absence of Best1.

3. The six novel mutations and high frequency of p.R255W suggest ethnical differences in the BEST1 mutation spectrum among Chinese patients. BEST1 gene screening and detailed clinical examinations help establishing a diagnosis of ARB.

4. We present a patient with a novel p.Met571Thr pathogenic variation associated with an autosomal-dominant vitreoretinochoroidopathy (ADVIRC) phenotype. Subretinal hemorrhage is a unique finding in ADVIRC patients and may correspond to peripheral exudative hemorrhagic chorioretinopathy.

5. hBest1's channel activity in human retinal pigment epithelium is significantly enhanced by adenosine triphosphate in a dose-dependent manner

6. two recurrent genetic variations of BEST1 in two Chinese patients with either juvenile-onset BVMD or adult-onset BVMD were identified in this study. These findings expand the mutation spectrum of BEST1 and may aid in genetic counseling as well as prenatal diagnoses of patients with BVMD.

7. These results revealed that the disease-causing mechanism of BEST1 mutations is centered on the indispensable role of BESTROPHIN1 in mediating the long speculated Ca(2+)-dependent Cl(-) current in retinal pigment epithelium.

8. We describe a highly recognizable and reproducible retinal phenotype associated with a specific BEST1 mutation-p.Ala243Val in vitelliform macular dystrophy.

9. We present a consanguineous family of five affected individuals with autosomal recessive bestrophinopathy and four confirmed carriers. Their pedigree was consistent with dominant inheritance and incomplete penetrance.

10. We have shown that the two novel combinations of compound heterozygous mutations p.R141H/p.M325T and p.R141H/p.I201T in the BEST1 gene can also lead to the autosomal recessive bestrophinopathy phenotype.

11. The findings in this family emphasize the previously noted variability of clinical manifestations in BEST1-associated autosomal dominant vitreoretinochoroidopathy (ADVIRC) and the relevance of FAF and NIA imaging. Cystoid macular edema and vascular leakage can be successfully treated using dorzolamide.

12. For patients with Best vitelliform macular dystrophy, single heterozygous BEST1 mutations were identified in 13 patients and compound heterozygous mutations were found in 3 patients. For patients with autosomal recessive bestrophinopathy, biallelic mutations were found in 13 probands and single mutant alleles in six patients. Overall, 36 disease-causing variants (20 novel mutations) of the BEST1 gene were identified.

13. Mutation in BEST1 has variable penetrance and expressivity, and can be uniocular.

14. We identified 7 BEST1 variants, 2 of which were new in 9 cases of Japanese patients with autosomal recessive bestrophinopathy.

15. Of the 225 genetic tests performed, 150 were for recessive IRD, and 75 were for dominant IRD. A positive molecular diagnosis was made in 70 (59%) of probands with recessive IRD and 19 (26%) probands with dominant IRD. Thirty-two novel variants were identified; among these, 17 sequence changes in four genes were predicted to be possibly or probably damaging including: ABCA4 (14), BEST1 (2), PRPH2 (1), and TIMP3

16. We describe the atypical phenotype and high intrafamilial variability associated with a new mutation in the BEST1 gene in an Italian family affected with Best vitelliform macular dystrophy.

17. A clinical picture similar to autosomal recessive bestrophinopathy can also be caused by a single heterozygous mutation in the BEST1 gene, such as the c.614T>C (p.I205T) variant in this family.

18. The secondary structure of Best1 and the effect of calcium have been described.

19. BVMD could present with other ocular disorders such as ACG and FCE. We also found 2 novel disease-causing mutations (p.Thr307Asp, p.Arg47His) of the BEST1 gene, one of which (p.Arg47His) has also been reported in adult-onset vitelliform macular dystrophy (AVMD)

20. Two previously unreported disease-associated variants in the BEST1 gene (p.Gly15Arg and p.Arg105Gly) were found in Slovenian patients with Best disease.

Mouse (Murine) Bestrophin 1 (BEST1) interaction partners

1. 14-3-3gamma promotes surface expression of Best1 channel in astrocytes through direct interaction.

2. Data suggest that the ion channels CaV1.3, bestrophin-1 and maxiK were identified as players in the regulation of photoreceptor outer segments (POS) phagocytosis by the retinal pigment epithelium (RPE).

3. Best1-mediated astrocytic glutamate activates the synaptic N-methyl-D-aspartate receptor (NMDAR) and modulates NMDAR-dependent synaptic plasticity.

4. Bestrophin-1 functions as an intracellular Cl channel which helps to accumulate and to release Ca(2+) from stores by conducting the counterion for Ca(2+).

5. Best1, located at the microdomains near the synaptic junctions, has a significantly high permeability to glutamate in vivo.

6. Results show that different mutations in Best1 cause differential effects on its localization and that this effect varies with the presence or absence of wild-type (WT) Best1.

7. Astrocytic glutamate via Best1 channel targets and activates synaptic NMDA receptors.

8. Upon activation of protease activated receptor 1 (PAR1), an increase in intracellular Ca2+ concentration leads to an opening of Best1 channels and subsequent release of glutamate in cultured astrocytes.

9. Ultrastructural analyses demonstrate that TREK-1 is preferentially localized at cell body and processes, whereas Best1 is mostly found in microdomains of astrocytes near synapses.

10. study reports that tonic inhibition in the cerebellum is due to GABA being released from glial cells by permeation through the Bestrophin 1 anion channel

11. SOX9, through interaction with microphthalmia-associated transcription factor (MITF) and OTX2, regulates BEST1 expression in the retinal pigment epithelium.

12. Retinal pigment bestrophin-1 possibly conducts Cl(-) as counter ion for Ca(2+) uptake into cytosolic Ca(2+) stores.

13. Data demonstrate that bestrophin 1 is localized in the endoplasmic reticulum (ER), where it interacts with the ER-Ca(2+) sensor and can enhance Ca(2+) signaling and activation of Ca(2+)-dependent Cl(-) (TMEM16A) and K(+) (SK4) channels.

14. cloning and characterization by combining biocomputational analyses and molecular genetic approaches

15. We suggest the loss of vision associated with Best vitelliform macular dystrophy is not caused by the same pathologic process as the diminished light peak, but is caused by an unidentified effect of best-1 [VMD2] on other cellular processes.

16. BEST1 may form the Ca2+-activated Cl(-) current, or it may be a component of a Cl(-) channel complex in epithelial tissues.

17. VMD2 is regulated by the MITF-TFE family through two E-boxes, with E-box 1 required for a direct interaction of MITF-TFE factors and E-box 2 for binding of the as yet unidentified factors

18. suggest a role of bestrophin 1 and 2 for Ca(2+) dependent Cl(-) secretion in mouse airways

19. This study provides the first characterization of the biophysical properties of mBest1 and a framework for the elucidation of the physiological role of bestrophins.

20. Repression of cell proliferation, induction of Ca(2+)-dependent Cl(-) conductance, and expression of Best1 occurs during mesenchymal-to-epithelial transition once renal collecting duct cells polarize and terminally differentiate.

Pig (Porcine) Bestrophin 1 (BEST1) interaction partners

1. Bestrophin-1 knock-down increases phagocytosis in primary porcine RPE cells.

2. Retinal pigment epithelium bestrophin-1 possibly conducts Cl(-) as counter ion for Ca(2+) uptake into cytosolic Ca(2+) stores.

3. examined the quaternary structure of native best-1 and found that it migrates as a single species with a Stokes radius of 7.3 nm, sedimentation coefficient (S20,w) of 4.9, and partial specific volume (nu) of 0.80 ml/g