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视网膜时钟驱动 Kcnv2 的表达,Kcnv2 是一种对视觉功能和视锥细胞存活至关重要的通道。

The retinal clock drives the expression of Kcnv2, a channel essential for visual function and cone survival.

机构信息

Department of Functional and Clinical Anatomy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

出版信息

Invest Ophthalmol Vis Sci. 2012 Oct 5;53(11):6947-54. doi: 10.1167/iovs.12-10234.

Abstract

PURPOSE

The gene Kcnv2 codes for the voltage-gated potassium channel subunit Kv8.2, which can coassemble with Kv2.1 subfamily members to constitute functional voltage-gated potassium channels. Mutations in the Kcnv2 gene result in a retinal disorder designated "cone dystrophy with supernormal rod response (CDSRR)," revealing that Kcnv2 is essential for visual processing and cone survival. The aim of this study was to determine whether expression of Kcnv2 and Kv2.1 is under circadian regulation and may thus contribute to the clock-driven adjustment of photoreceptor function.

METHODS

Expression of the genes was recorded in preparations of the whole retina and microdissected retinal neurons by using quantitative polymerase chain reaction and Western blot.

RESULTS

The transcript levels of Kcnv2 and Kv2.1 in preparations of whole retina and photoreceptor cells were found to display daily rhythms, with elevated values during the night. For Kcnv2 this rhythm was shown to evoke a corresponding rhythm in Kv8.2, the protein product of this gene. The daily changes in retinal Kcnv2 and Kv2.1 mRNA levels persisted under constant darkness and are therefore driven by the endogenous retinal clock system, which itself is entrained by light.

CONCLUSIONS

The present data provide evidence that the transcriptional regulation of Kcnv2 and Kv2.1 is a way through which the retinal clock system drives the functional adaptation of visual function to the marked daily changes in environmental lighting conditions.

摘要

目的

基因 Kcnv2 编码电压门控钾通道亚基 Kv8.2,它可以与 Kv2.1 亚家族成员共同组装,构成功能性电压门控钾通道。Kcnv2 基因的突变导致一种被称为“超正常棒状反应的锥体细胞营养不良症(CDSRR)”的视网膜疾病,表明 Kcnv2 对视觉处理和锥体细胞存活至关重要。本研究旨在确定 Kcnv2 和 Kv2.1 的表达是否受昼夜节律调节,从而可能有助于光感受器功能的时钟驱动调节。

方法

通过定量聚合酶链反应和 Western blot 记录整个视网膜和微分离视网膜神经元中基因的表达。

结果

在整个视网膜和光感受器细胞的制剂中,Kcnv2 和 Kv2.1 的转录水平显示出昼夜节律,夜间值升高。对于 Kcnv2,这种节律会引发该基因的蛋白质产物 Kv8.2 的相应节律。在持续黑暗下,视网膜 Kcnv2 和 Kv2.1 mRNA 水平的昼夜变化仍然存在,因此是由内源性视网膜时钟系统驱动的,而内源性视网膜时钟系统本身又受到光的调节。

结论

本研究数据提供了证据,表明 Kcnv2 和 Kv2.1 的转录调控是视网膜时钟系统驱动视觉功能适应环境光照条件明显昼夜变化的一种方式。

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