Shining New Light on the Structural Determinants of Cardiac Couplon Function: Insights From Ten Years of Nanoscale Microscopy.
Shining New Light on the Structural Determinants of Cardiac Couplon Function: Insights From Ten Years of Nanoscale Microscopy.
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DOI：
10.3389/fphys.2018.01472
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发表时间：
2018
影响因子：
4
通讯作者：
Soeller C
中科院分区：
文献类型：
--
作者：
Jayasinghe I;Clowsley AH;de Langen O;Sali SS;Crossman DJ;Soeller C
在心肌病发病过程中，膜和蛋白质聚集模式的重塑重新引起了人们对心肌细胞中这些结构的空间可视化的兴趣。在过去十年中，单分子（超分辨率）成像和断层电子显微镜工具的巧合出现，导致了对偶联体结构特征的许多新的观察，偶联体是心脏兴奋-收缩耦合的主要部位。特别是，超分辨率和层析电子显微摄影已经修正和完善了经典的关于偶联子、t小管和健康和衰竭心脏中主要钙处理蛋白组织的纳米几何形状的观点。这些方法也允许可视化一些特征，这些特征太小，无法用传统的显微镜工具检测到。随着新的分析能力，如单蛋白制图、原位蛋白定量、相关和活细胞成像，我们现在观察到在心脏生物物理研究学科中采用这些研究工具的前所未有的兴趣。在本文中，我们回顾了这些工具对理解心脏偶联子的结构和功能所带来的新见解的深度。我们概述了这些实验中仍然存在的主要挑战以及这些技术将使之成为可能的新兴研究途径。
Remodelling of the membranes and protein clustering patterns during the pathogenesis of cardiomyopathies has renewed the interest in spatial visualisation of these structures in cardiomyocytes. Coincidental emergence of single molecule (super-resolution) imaging and tomographic electron microscopy tools in the last decade have led to a number of new observations on the structural features of the couplons, the primary sites of excitation-contraction coupling in the heart. In particular, super-resolution and tomographic electron micrographs have revised and refined the classical views of the nanoscale geometries of couplons, t-tubules and the organisation of the principal calcium handling proteins in both healthy and failing hearts. These methods have also allowed the visualisation of some features which were too small to be detected with conventional microscopy tools. With new analytical capabilities such as single-protein mapping, in situ protein quantification, correlative and live cell imaging we are now observing an unprecedented interest in adapting these research tools across the cardiac biophysical research discipline. In this article, we review the depth of the new insights that have been enabled by these tools toward understanding the structure and function of the cardiac couplon. We outline the major challenges that remain in these experiments and emerging avenues of research which will be enabled by these technologies.
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影响因子：
3.7
作者：
Crossman DJ;Ruygrok PN;Soeller C;Cannell MB
通讯作者：
Cannell MB
影响因子：
56.9
作者：
Bates, Mark;Huang, Bo;Zhuang, Xiaowei
通讯作者：
Zhuang, Xiaowei
影响因子：
3.4
作者：
Franzini-Armstrong, C;Protasi, F;Ramesh, V
通讯作者：
Ramesh, V
影响因子：
10.8
作者：
Balijepalli, RC;Lokuta, AJ;Kamp, TJ
通讯作者：
Kamp, TJ
影响因子：
2.7
作者：
Cannell, M. B.;Crossman, D. J.;Soeller, C.
通讯作者：
Soeller, C.