Functional heterogeneity of mutant rhodopsins responsible for autosomal dominant retinitis pigmentosa.
Functional heterogeneity of mutant rhodopsins responsible for autosomal dominant retinitis pigmentosa.
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导致常染色体显性视网膜色素变性的突变视紫红质的功能异质性。
DOI：
10.1073/pnas.88.19.8840
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发表时间：
1991
影响因子：
11.1
通讯作者：
J. Nathans
中科院分区：
文献类型：
--
作者：
C. Sung;B. Schneider;N. Agarwal;D. Papermaster;J. Nathans
通过将克隆的cDNA转染组织培养细胞，产生了13种常染色体显性视网膜色素变性（ADRP）的突变型视紫红质。三个变种人[一级：Phe-45-Leu、Gln-344-终止（缺失C-末端位置344-348）和Pro-347-Leu]在产量、用11-顺式-视黄醛的可再生性和质膜定位方面类似于野生型视紫红质。十个变种人[二级：Thr-17-Met、Pro-23-His、Thr-58-Arg、瓦尔-87-Asp、Gly-89-Asp、Gly-106-Trp、Arg-135-Leu、Arg-135-Trp、Tyr-178-Cys和Asp-190-Gly]累积至显著较低水平，用11-顺式-视黄醇再生或根本不再生，并被低效地转运至质膜，主要保留在内质网中。这些数据表明，有至少两个不同的生化缺陷与不同的视紫红质突变体在ADRP。
Thirteen mutant rhodopsins responsible for autosomal dominant retinitis pigmentosa (ADRP) have been produced by transfection of cloned cDNA into tissue culture cells. Three mutants [class I: Phe-45----Leu, Gln-344----termination (deletion of C-terminal positions 344-348), and Pro-347----Leu] resemble wild-type rhodopsin in yield, regenerability with 11-cis-retinal, and plasma membrane localization. Ten mutants [class II: Thr-17----Met, Pro-23----His, Thr-58----Arg, Val-87----Asp, Gly-89----Asp, Gly-106----Trp, Arg-135----Leu, Arg-135----Trp, Tyr-178----Cys, and Asp-190----Gly] accumulate to significantly lower levels, regenerate with 11-cis-retinal variably or not at all, and are transported inefficiently to the plasma membrane, remaining primarily in the endoplasmic reticulum. These data suggest that there are at least two distinct biochemical defects associated with different rhodopsin mutants in ADRP.