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视杆光感受器形态发生与疾病的结构和分子基础。

Structural and molecular bases of rod photoreceptor morphogenesis and disease.

作者信息

Wensel Theodore G, Zhang Zhixian, Anastassov Ivan A, Gilliam Jared C, He Feng, Schmid Michael F, Robichaux Michael A

机构信息

Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.

Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.

出版信息

Prog Retin Eye Res. 2016 Nov;55:32-51. doi: 10.1016/j.preteyeres.2016.06.002. Epub 2016 Jun 22.

Abstract

The rod cell has an extraordinarily specialized structure that allows it to carry out its unique function of detecting individual photons of light. Both the structural features of the rod and the metabolic processes required for highly amplified light detection seem to have rendered the rod especially sensitive to structural and metabolic defects, so that a large number of gene defects are primarily associated with rod cell death and give rise to blinding retinal dystrophies. The structures of the rod, especially those of the sensory cilium known as the outer segment, have been the subject of structural, biochemical, and genetic analysis for many years, but the molecular bases for rod morphogenesis and for cell death in rod dystrophies are still poorly understood. Recent developments in imaging technology, such as cryo-electron tomography and super-resolution fluorescence microscopy, in gene sequencing technology, and in gene editing technology are rapidly leading to new breakthroughs in our understanding of these questions. A summary is presented of our current understanding of selected aspects of these questions, highlighting areas of uncertainty and contention as well as recent discoveries that provide new insights. Examples of structural data from emerging imaging technologies are presented.

摘要

视杆细胞具有极其特殊的结构,使其能够执行检测单个光量子的独特功能。视杆细胞的结构特征以及高度放大的光检测所需的代谢过程似乎使视杆细胞对结构和代谢缺陷特别敏感,因此大量基因缺陷主要与视杆细胞死亡相关,并导致致盲性视网膜营养不良。多年来,视杆细胞的结构,尤其是被称为外段的感觉纤毛的结构,一直是结构、生化和遗传分析的主题,但视杆细胞形态发生以及视杆细胞营养不良中细胞死亡的分子基础仍知之甚少。成像技术(如冷冻电子断层扫描和超分辨率荧光显微镜)、基因测序技术和基因编辑技术的最新进展正在迅速引领我们在理解这些问题上取得新突破。本文总结了我们目前对这些问题选定方面的理解,突出了不确定性和争议领域以及提供新见解的最新发现。还展示了来自新兴成像技术的结构数据示例。

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