ABCA1 p.Tyr1767Asp
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PMID: 23087442
[PubMed]
Sorrenson B et al: "Functional rescue of mutant ABCA1 proteins by sodium 4-phenylbutyrate."
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Nine different ABCA1 mutants (p.A594T, p.I659V, p.R1068H, p.T1512M, p.Y1767D, p.N1800H, p.R2004K, p.A2028V, p.Q2239N) expressed in HEK293 cells, displaying different degrees of mislocalization to the plasma membrane and discrete impacts on cholesterol efflux, were subject to treatment with 4-PBA.
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ABCA1 p.Tyr1767Asp 23087442:16:70
status: NEW54 We identified a further three novel mutations, p.A594T, p.Y1767D, and p.Q2239N, and these were also included in this study. We hypothesized that efflux function would be improved for mutants that are dysfunctional as a result of protein mislocation.
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ABCA1 p.Tyr1767Asp 23087442:54:58
status: NEW73 Both media were RESULTS ABCA1 mutants with impaired localization have reduced cholesterol efflux function We identified three novel ABCA1 variants, p.A594T, p.Y1767D, and p.Q2239N, in heterozygote form in three individuals with HDL-C levels of 0.61, 0.17, and 0.37 mmol/L, respectively.
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ABCA1 p.Tyr1767Asp 23087442:73:162
status: NEW74 The individual heterozygote for p.Y1767D was also heterozygote for the p.N1800H ABCA1 mutation.
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ABCA1 p.Tyr1767Asp 23087442:74:34
status: NEW77 Investigation of the six uncharacterized mutations in transfected HEK293 cells showed the p.A594T, p.I659V, p.Y1767D, p.R2004K, and p.A2028V mutants to have various degrees of mislocalization (Fig. 2A).
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ABCA1 p.Tyr1767Asp 23087442:77:110
status: NEW79 Areas of mislocalized ABCA1-GFP are indicated by arrows in Fig. 2A with the p.Y1767D and R2004K mutants being the most affected.
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ABCA1 p.Tyr1767Asp 23087442:79:78
status: NEW80 The mislocalization of mutant ABCA1s was associated with a reduced cholesterol efflux function compared with wild-type-GFP ABCA1 (Fig. 2B) with the p.Y1767D mutant being the most affected (30.3% the efflux of wild-type).
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ABCA1 p.Tyr1767Asp 23087442:80:150
status: NEW109 Upon 4-PBA treatment, efflux function was significantly increased relative to the untreated level for the p.R1068H, p.T1512M, p.Y1767D, p.N1800H, p.R2004K, and p.A2028V mutants (Fig. 3B).
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ABCA1 p.Tyr1767Asp 23087442:109:128
status: NEW112 Treatment with 4-PBA induced a significant increase in colocalization for the p.A594T, p.R1068H, p.T1512M, p.Y1767D, p.N1800H, and p.R2004K mutants. Treatment with 4-PBA did not affect the colocalization of the wild-type ABCA1-GFP protein (supplementary Fig. II).
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ABCA1 p.Tyr1767Asp 23087442:112:109
status: NEW125 mislocated mutants, p.Y1767D, and p.N1800H, showed a restored efflux function that was equivalent to wild-type untreated cells.
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ABCA1 p.Tyr1767Asp 23087442:125:22
status: NEW164 For example, the p.Y1767D mutant showed a much enhanced localization and dramatic increase in cholesterol efflux after 4-PBA treatment whereas the efflux function for the p.R1068H mutant remained low despite showing a similar enhancement in localization.
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ABCA1 p.Tyr1767Asp 23087442:164:19
status: NEW