Recent advances in understanding the ryanodine receptor calcium release channels and their role in calcium signalling.
Recent advances in understanding the ryanodine receptor calcium release channels and their role in calcium signalling.
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DOI：
10.12688/f1000research.16434.1
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发表时间：
2018-01-01
期刊：
影响因子：
--
通讯作者：
Casarotto, Marco G
中科院分区：
文献类型：
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作者：
Dulhunty, Angela F;Beard, Nicole A;Casarotto, Marco G
兰尼碱受体钙释放通道是骨骼肌、心脏和许多其他组织（包括中枢神经系统、淋巴细胞、胃、肾、肾上腺、卵巢、睾丸、胸腺和肺）细胞质 Ca 2+ 信号传导的核心。这种离子通道蛋白体积巨大（超过 2.2 MDa），其结构一直无法详细确定，直到最近冷冻电子显微镜的发展以接近原子分辨率揭示了其大部分结构。这种高分辨率结构的出现为理解离子通道功能提供了过去 30 年来最重大的进展。我们现在可以可视化形成离子通道功能重要调节剂结合位点的单个氨基酸残基的分子环境，并确定其在 Ca 2+ 信号传导中的作用。重要的是，该结构揭示了许多缺失和点突变的结构环境，这些缺失和点突变破坏了骨骼肌病、心肌病和神经病中的 Ca 2+ 信号传导。这些影响对于我们理解离子通道功能的分子基础以及设计抵消兰尼碱受体相关疾病影响的疗法至关重要。
The ryanodine receptor calcium release channel is central to cytoplasmic Ca 2+ signalling in skeletal muscle, the heart, and many other tissues, including the central nervous system, lymphocytes, stomach, kidney, adrenal glands, ovaries, testes, thymus, and lungs. The ion channel protein is massive (more than 2.2 MDa) and has a structure that has defied detailed determination until recent developments in cryo-electron microscopy revealed much of its structure at near-atomic resolution. The availability of this high-resolution structure has provided the most significant advances in understanding the function of the ion channel in the past 30 years. We can now visualise the molecular environment of individual amino acid residues that form binding sites for essential modulators of ion channel function and determine its role in Ca 2+ signalling. Importantly, the structure has revealed the structural environment of the many deletions and point mutations that disrupt Ca 2+ signalling in skeletal and cardiac myopathies and neuropathies. The implications are of vital importance to our understanding of the molecular basis of the ion channel's function and for the design of therapies to counteract the effects of ryanodine receptor-associated disorders.