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在鞭毛内信号转导中钙扩散及其快速缓冲的作用。

On the role of calcium diffusion and its rapid buffering in intraflagellar signaling.

机构信息

Serbian Academy of Science and Arts, Belgrade, Serbia.

Faculty of Technical Sciences, University of Novi Sad, Novi Sad, Serbia.

出版信息

Eur Biophys J. 2023 Nov;52(8):705-720. doi: 10.1007/s00249-023-01685-6. Epub 2023 Oct 18.

DOI:10.1007/s00249-023-01685-6
PMID:37851099
Abstract

We have considered the realistic mechanism of rapid Ca (calcium ion) buffering within the wave of calcium ions progressing along the flagellar axoneme. This buffering is an essential part of the Ca signaling pathway aimed at controlling the bending dynamics of flagella. It is primarily achieved by the mobile region of calmodulin molecules and by stationary calaxin, as well as by the part of calmodulin bound to calcium/calmodulin-dependent kinase II and kinase C. We derived and elaborated a model of Ca diffusion within a signaling wave in the presence of these molecules which rapidly buffer Ca. This approach has led to a single nonlinear transport equation for the Ca wave that contains the effects brought about by both as necessary buffers for signaling. The presence of mobile buffer calmodulin gives rise to a transport equation that is not strictly diffusive but also exhibits a sink-like effect. We solved straightforwardly the final transport equation in an analytical framework and obtained the implied function of calcium concentration. The effective diffusion coefficient depends on local Ca concentration. It is plausible that these buffers' presence can impact Ca wave speed and shape, which are essential for decoding Ca signaling in flagella. We present the solution of the transport equation for a few specified cases with physiologically reasonable sets of parameters involved.

摘要

我们考虑了钙离子波中快速钙离子缓冲的实际机制,钙离子波沿着鞭毛轴突传播。这种缓冲是钙信号通路的一个重要组成部分,旨在控制鞭毛的弯曲动力学。它主要通过钙调蛋白分子的可移动区域和固定的钙调蛋白结合蛋白,以及与钙/钙调蛋白依赖性激酶 II 和蛋白激酶 C 结合的钙调蛋白部分来实现。我们推导出并详细阐述了一个存在这些快速缓冲钙离子的信号波内钙离子扩散模型。这种方法导致了一个单一的非线性输运方程,其中包含了两个信号缓冲所带来的影响。可移动缓冲钙调蛋白的存在导致输运方程不仅具有扩散性质,还具有汇的性质。我们在解析框架中直接求解了最终的输运方程,并得到了隐含的钙浓度函数。有效扩散系数取决于局部钙浓度。这些缓冲剂的存在可能会影响钙波的速度和形状,这对鞭毛中的钙信号解码至关重要。我们给出了几个特定情况下的输运方程解,涉及到具有生理合理性的参数集。

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本文引用的文献

1
Calaxin stabilizes the docking of outer arm dyneins onto ciliary doublet microtubule in vertebrates.Calaxin 稳定了脊椎动物中外臂动力蛋白与纤毛二联体微管的对接。
Elife. 2023 Apr 14;12:e84860. doi: 10.7554/eLife.84860.
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Modeling Microtubule Counterion Distributions and Conductivity Using the Poisson-Boltzmann Equation.使用泊松-玻尔兹曼方程对微管抗衡离子分布和电导率进行建模。
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How signals of calcium ions initiate the beats of cilia and flagella.
钙离子信号如何引发纤毛和鞭毛的摆动。
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Outer dense fibers stabilize the axoneme to maintain sperm motility.外致密纤维稳定轴丝以维持精子运动能力。
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Human sperm steer with second harmonics of the flagellar beat.人类精子通过鞭毛拍打的二次谐波进行导向。
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Functional anatomy of the mammalian sperm flagellum.哺乳动物精子鞭毛的功能解剖学。
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Microtubule doublets are double-track railways for intraflagellar transport trains.微管二联体是鞭毛内运输列车的双轨铁路。
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Calmodulin as a major calcium buffer shaping vesicular release and short-term synaptic plasticity: facilitation through buffer dislocation.钙调蛋白作为塑造囊泡释放和短期突触可塑性的主要钙缓冲剂:通过缓冲剂错位实现易化作用
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