1 is caused by mutations in the gene encoding
bestrophin.
2 Here, we show that
bestrophin 1 (BEST1) but not LRRC8A is crucial for volum
3 Mutations in
bestrophin 1 (BEST1) cause certain eye diseases.
4 Mutations in
bestrophin 1 (BEST1) cause macular degenerative disorder
5 higher expression in the periphery included
bestrophin 1 (BEST1), transcription factor RNA binding m
6 Mutations in the human
bestrophin 1 (hBest1) chloride channel cause Best vitell
7 Human
Bestrophin 1 (hBest1) is a calcium-activated chloride ch
8 n isolates with antibodies specific to human
bestrophin 1 (hBest1) showed that hBest1 protein was exp
9 aob) and abnormally release GABA through the
bestrophin 1 channel.
10 Mutations in the
bestrophin-
1 (Best1) gene are linked to several kinds of
11 Mutations in BEST1, encoding
bestrophin-
1 (Best1), cause Best vitelliform macular dys
12 Human
bestrophin-
1 (hBest1) is a calcium-activated chloride ch
13 in the founding member of the family, human
bestrophin-
1 (hBest1), are responsible for a form of ear
14 ction in the Cl(-) channel function of human
bestrophin-
1 (hBest1), but some patients with BVMD who h
15 y mutations in a chloride ion channel, human
bestrophin-
1 (hBest1).
16 Mutations in human
bestrophin-
1 (VMD2) are genetically linked to a juvenile
17 Mutations in
bestrophin-
1 are increasingly recognized as an important
18 not impair the formation of active wild-type
bestrophin-
1 channels, consistent with the recessive nat
19 Best disease, cotransfection with wild-type
bestrophin-
1 did not impair the formation of active wild
20 L140V and p.D228N) caused mislocalization of
bestrophin-
1 from the basolateral membrane to the cytopl
21 observed in vivo and, thus, implies loss of
bestrophin-
1 function in cmr1-dogs and Y(29)X-affected p
22 Bestrophin-
1 gene (BEST1) mutations are responsible for
23 We propose that ARB is the null phenotype of
bestrophin-
1 in humans.
24 Bestrophin-
1 is preferentially expressed at the basolate
25 One potential role of
Bestrophin-
1 is to trigger an increase in the standing p
26 ruct that would express neurogenin1 from RPE
bestrophin-
1 promoter or neurogenin3 from RPE65 promoter
27 The physiological function of
bestrophin-
1 remains poorly understood although its hete
28 ch-clamping of HEK293 cells transfected with
bestrophin-
1 to measure the Cl(-) current.
29 One of these, BEST1, encodes
bestrophin-
1, a protein that when mutated causes Best ma
30 alcium-activated chloride channels (TMEM16A,
Bestrophin-
1, ClC2, and SLC26A9), both features striking
31 The transmembrane protein
bestrophin-
1, encoded by BEST1, is located at the basola
32 Here, we describe four missense mutations in
bestrophin-
1, three that we believe are previously unrep
33 hannel activity and cellular localization of
bestrophin-
1.
34 kcc1) and the Ca(2+)-activated anion channel
Bestrophin 2 (Best2), as well as glycoprotein accumulati
35 Bestrophin-
2 (Best2), a putative Cl(-) channel is expres
36 Mice deficient in the bicarbonate channel
bestrophin-
2 (Best2), however, exhibit a lower IOP despi
37 igated the role of a candidate CaCC protein,
bestrophin-
2 (Best2), using Best2-/- mice.
38 matically replaced every amino acid in mouse
bestrophin-
2 (mBest2) between positions 69 and 104 with
39 inantly expressed in RPE/choroid and encodes
bestrophin,
a 580-amino acid protein of 66 kDa.
40 ated in Best macular dystrophy (BMD) encodes
bestrophin,
a 68-kDa basolateral plasma membrane protein
41 Neither wild-type (wt) nor mutant
bestrophin affected the a- or b-waves of the ERG.
42 cells by adenovirus-mediated gene transfer,
bestrophin again was determined by confocal microscopy a
43 VMD2 encodes
bestrophin,
an oligomeric chloride channel that is prefe
44 Protein-protein interaction between
bestrophin and PP2Ac and the structural subunit of PP2A,
45 ltured for 21 days were harvested to compare
bestrophin and RPE65 mRNA expression.
46 phin complex from RPE lysates and identified
bestrophin and the beta-catalytic subunit of protein pho
47 e heart, including CFTR, ClC-2, ClC-3, CLCA,
Bestrophin,
and TMEM16A.
48 Cytoplasmic calcium (Ca(2+)) activates the
bestrophin anion channel, allowing chloride ions to flow
49 The
bestrophins are a newly described family of anion channe
50 Bestrophins are a newly identified family of Cl(-) chann
51 interpreted in terms of the hypotheses that
bestrophins are Cl(-) channels and regulators of Ca sign
52 Recently, it has been proposed that
bestrophins are Cl- channels and that the putative secon
53 This study provides evidence that the
bestrophins are expressed in pancreatic duct cells and,
54 It has been suggested that
bestrophins are multifunctional proteins: they may regul
55 We conclude that
bestrophins are the first molecularly identified Cl- cha
56 We conclude that
bestrophins are volume sensitive and that they could pla
57 Bestrophin calcium-activated chloride channels (CaCCs) r
58 Several chloride channels including TMEM16,
bestrophin,
CFTR, CLCN2 and CLCA1, are also expressed in
59 provide the first structural analysis of the
bestrophin channel family.
60 nction further, we immunoaffinity purified a
bestrophin complex from RPE lysates and identified bestr
61 kage and a approximately 70-80% reduction in
bestrophin current.
62 es in extracellular osmolarity increased the
bestrophin currents slightly, but this was difficult to
63 photoreceptor discs, we investigated whether
bestrophin currents were affected by cell volume.
64 that have a single "selectivity filter," in
bestrophin,
distinct regions of the pore govern anion-vs
65 curs before activation of bestrophin or that
bestrophin does not directly generate the LP conductance
66 The human genome codes for four
bestrophins,
each of which confers a distinctive plasma
67 Recently, the
bestrophin family of proteins have been proposed as a po
68 ls at the apical membrane are members of the
bestrophin family which, like CFTR, are also permeable t
69 Cl- channels, which included members of the
bestrophin family.
70 here that human, Drosophila, and C. elegans
bestrophins form oligomeric chloride channels, and that
71 We cloned two
bestrophins from Xenopus oocytes, which express high lev
72 BEST1 (alias VMD2), the
bestrophin gene causally associated with BMD, was evalua
73 Mutations in the
Bestrophin gene were shown in patients affected with VMD
74 We predict that
bestrophin has six transmembrane domains with the conser
75 In the present study, the expression of
bestrophins has been investigated in the cystic fibrosis
76 Although
bestrophins have been shown clearly to be Cl(-) ion chan
77 There are multiple
bestrophin homologues in the human, Drosophila, and Caen
78 Wt
bestrophin,
however, increased the c-wave and fast oscil
79 Immunohistochemical localization of
bestrophin in a series of 22 unaffected eyes revealed a
80 Bestrophin in human RPE partitioned in the detergent pha
81 ochemistry could not confirm the presence of
Bestrophin in normal human retina.
82 Our findings reveal a novel function of
bestrophin in regulation of Ca(V) channels and suggest a
83 Purified PP2A effectively dephosphorylated
bestrophin in vitro.
84 sensitive control of ion selectivity in the
bestrophins,
including reversal of anion/cation selectiv
85 echanism in C termini may be universal among
bestrophins investigated in the study.
86 Bestrophin is a 68-kDa basolateral plasma membrane prote
87 Recently it was proposed that
bestrophin is a chloride channel responsible for generat
88 These data suggest that
bestrophin is in the signal transduction pathway that mo
89 phosphorylation, and that phosphorylation of
bestrophin is in turn regulated by PP2A.
90 g of macaque and porcine eyes indicated that
bestrophin is localized at the basolateral plasma membra
91 oligomeric chloride channels, and that human
bestrophin is sensitive to intracellular calcium.
92 Bestrophin is thought to be the Cl channel that generate
93 The function of
bestrophin is unknown.
94 Expression of
bestrophins is strongly correlated with the function of
95 All of the cell lines expressed
bestrophin mRNA by reverse transcription-PCR, but not on
96 ed positive identification of all four human
bestrophin mRNAs.
97 Bestrophin or
bestrophin mutants (W93C or R218C) were overexpressed in
98 Bestrophin or bestrophin mutants (W93C or R218C) were ov
99 explants, but expressed very little mRNA for
bestrophin or RPE65.
100 ing LP amplitude occurs before activation of
bestrophin or that bestrophin does not directly generate
101 model of BMD and to determine the effects of
bestrophin overexpression on the RPE-generated component
102 of bestrophin suggests the possibility that
bestrophin plays a role in generating the altered electr
103 smembrane domain participates in forming the
bestrophin pore.
104 hannels, as was previously thought, and that
bestrophins,
previously prime candidates for Ca(2+)-acti
105 The expression of
bestrophin protein and mRNA was evaluated by immunohisto
106 Topographic differences in the levels of
bestrophin protein may in part explain the propensity fo
107 structure of the anion conduction pathway of
bestrophins provides insights into how mutations produce
108 LP response functions were unaffected by
bestrophin R218C but were significantly altered by bestr
109 Because overexpression of wt
bestrophin shifted luminance response but did not alter
110 -binding domain that is not present in other
bestrophin subtypes.
111 basolateral plasma membrane localization of
bestrophin suggests the possibility that bestrophin play
112 Bestrophin,
the protein product of the VMD gene, has fou
113 ss a range of stimuli were not altered by wt
bestrophin,
though the luminance response function was d
114 Bestrophins (
VMD2, VMD2L1, VMD2L2, and VMD2L3) are a new
115 phin R218C but were significantly altered by
bestrophin W93C.
116 Bestrophin was confined to the basolateral plasma membra
117 Bestrophin was phosphorylated when expressed in RPE-J ce
118 The C-terminal cytoplasmic domain of
bestrophin was sufficient for the interaction with PP2A
119 ne on chromosome 11q13, encoding the protein
bestrophin,
was identified.
120 To characterize
bestrophin,
we initially probed the retinal pigment epit
121 To facilitate studies of
bestrophin,
we produced both rabbit polyclonal and mouse
122 Four of these mutant
bestrophins were coexpressed with the wild type and each
123 The Xenopus
bestrophins were expressed in a variety of tissues.
124 When Xenopus
bestrophins were heterologously expressed in human embry
125 The prediction of enzymatic activity for
bestrophin,
whose gene is mutated in Best macular dystro