纳米连接:Ca2+信号的特异性需要细胞膜内接触位点的纳米级结构

IF 4.3 2区 生物学 Q2 CELL BIOLOGY Cell calcium Pub Date : 2023-11-19 DOI:10.1016/j.ceca.2023.102837
Nicola Fameli , Cornelis van Breemen , Klaus Groschner
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引用次数: 0

摘要

Ca2+信号的时空定义涉及信号复合物在sarco/endoplasmic网(SR/ER)和质膜(PM)之间接触位点的纳米结构内的组装。虽然对连接信号元件的精确空间组装和定位的要求已经得到了充分的证明,但纳米级膜结构本身作为信号单元的离子反射限制的作用仍然难以捉摸。利用Na+/Ca2+ exchange -1 / SR/ER Ca2+ atpase -2介导的ER Ca2+再填充过程作为连接信号范式,我们在这里提供了连接膜结构不可或缺的细胞功能的第一个证据。我们的随机建模方法表明,结ER Ca2+再填充仅在纳米级膜间距下进行,结宽度和信号传导效率之间存在很强的反比关系。我们的模型预测了连接Ca2+信号的分解与反射膜约束的损失。此外,我们考虑Ca2+和磷脂膜表面之间的相互作用,这可能支持界面Ca2+运输和促进受体靶向。细胞器- pm接触时分子和纳米尺度膜组织的改变是病理生理学中的一个新概念。
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Nanojunctions: Specificity of Ca2+ signaling requires nano-scale architecture of intracellular membrane contact sites

Spatio-temporal definition of Ca2+ signals involves the assembly of signaling complexes within the nano-architecture of contact sites between the sarco/endoplasmic reticulum (SR/ER) and the plasma membrane (PM). While the requirement of precise spatial assembly and positioning of the junctional signaling elements is well documented, the role of the nano-scale membrane architecture itself, as an ion-reflecting confinement of the signalling unit, remains as yet elusive. Utilizing the Na+/Ca2+ Exchanger-1 / SR/ER Ca2+ ATPase-2-mediated ER Ca2+ refilling process as a junctional signalling paradigm, we provide here the first evidence for an indispensable cellular function of the junctional membrane architecture. Our stochastic modeling approach demonstrates that junctional ER Ca2+ refilling operates exclusively at nano-scale membrane spacing, with a strong inverse relationship between junctional width and signaling efficiency. Our model predicts a breakdown of junctional Ca2+ signaling with loss of reflecting membrane confinement. In addition we consider interactions between Ca2+ and the phospholipid membrane surface, which may support interfacial Ca2+ transport and promote receptor targeting. Alterations in the molecular and nano-scale membrane organization at organelle-PM contacts are suggested as a new concept in pathophysiology.

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来源期刊
Cell calcium
Cell calcium 生物-细胞生物学
CiteScore
8.70
自引率
5.00%
发文量
115
审稿时长
35 days
期刊介绍: Cell Calcium covers the field of calcium metabolism and signalling in living systems, from aspects including inorganic chemistry, physiology, molecular biology and pathology. Topic themes include: Roles of calcium in regulating cellular events such as apoptosis, necrosis and organelle remodelling Influence of calcium regulation in affecting health and disease outcomes
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