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小鼠视杆光感受器中鸟苷三磷酸酶缺陷型视锥转导素的表达诱导环磷酸鸟苷磷酸二酯酶下调。

Downregulation of cGMP phosphodiesterase induced by expression of GTPase-deficient cone transducin in mouse rod photoreceptors.

作者信息

Raport C J, Lem J, Makino C, Chen C K, Fitch C L, Hobson A, Baylor D, Simon M I, Hurley J B

机构信息

Department of Biochemistry and Howard Hughes Medical Institute, Seattle, Washington 98195.

出版信息

Invest Ophthalmol Vis Sci. 1994 Jun;35(7):2932-47.

PMID:8206711
Abstract

PURPOSE

Photoexcitation of vertebrate retinal rod photoreceptors stimulates GTP binding to the transducin alpha subunit. Like other GTP-binding proteins, transducin restores itself to an inactive form by hydrolyzing its bound GTP. The role of GTP hydrolysis in phototransduction was investigated.

METHODS

A mutant form of cone transducin alpha deficient in its ability to hydrolyze bound GTP was expressed in mouse rod photoreceptors.

RESULTS

Expression of the mutant cone transducin alpha at levels threefold to sixfold higher than endogenous rod transducin alpha led to a specific depletion of the transducin target, cGMP phosphodiesterase, and a decrease in the cGMP level. Suction electrode recordings revealed abnormally prolonged flash responses, decreased maximal response amplitudes, and a shift in the stimulus-response relation to higher flash strengths.

CONCLUSIONS

Rods expressing high levels of GTPase-deficient cone transduction alpha have reduced levels of phosphodiesterase catalytic subunits and cGMP. These changes are associated with prolonged flash responses, reduced dark current, and decreased sensitivity to light.

摘要

目的

对脊椎动物视网膜视杆光感受器进行光激发可刺激鸟苷三磷酸(GTP)与转导素α亚基结合。与其他GTP结合蛋白一样,转导素通过水解其结合的GTP恢复到无活性形式。研究了GTP水解在光转导中的作用。

方法

在小鼠视杆光感受器中表达一种缺乏水解结合GTP能力的视锥转导素α突变体。

结果

突变体视锥转导素α的表达水平比内源性视杆转导素α高3至6倍,导致转导素靶标cGMP磷酸二酯酶特异性耗竭,cGMP水平降低。吸盘电极记录显示闪光反应异常延长、最大反应幅度降低,以及刺激-反应关系向更高闪光强度偏移。

结论

表达高水平GTP酶缺陷型视锥转导素α的视杆细胞中磷酸二酯酶催化亚基和cGMP水平降低。这些变化与闪光反应延长、暗电流降低和光敏感性降低有关。

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