Kinetics of rhodopsin deactivation and its role in regulating recovery and reproducibility of rod photoresponse.
Kinetics of rhodopsin deactivation and its role in regulating recovery and reproducibility of rod photoresponse.
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DOI：
10.1371/journal.pcbi.1001031
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发表时间：
2010-12-16
影响因子：
4.3
通讯作者：
DiBenedetto E
中科院分区：
文献类型：
--
作者：
Caruso G;Bisegna P;Lenoci L;Andreucci D;Gurevich VV;Hamm HE;DiBenedetto E
脊椎动物光转导中的单光子响应（SPR）受R* 在其生命周期中的动力学调节，包括磷酸化的随机数目、催化活性和在每个磷酸化水平上的随机停留时间。由于这种随机性，预期电响应是固有可变的。然而，SPR是高度可再现的。赋予SPR如此低的可变性的机制尚未完全理解。视紫红质失活的动力学研究的基础上的视紫红质激活和失活的生物化学的连续时间马尔可夫链（CTMC），与光转导的时空模型接口。从野生型和突变小鼠的光响应数据中提取模型参数，具有可变数目的磷酸化位点，并且使用相同的参数集，模型再现WT和突变体响应。变异性的来源被分解成它的组成部分，通过询问是否是一个随机数的关闭步骤，步骤之间的随机逗留时间，或两者兼而有之，引起已知的变异性。该模型表明，只有在每个磷酸化状态的逗留时间的随机性有助于响应的变异系数（CV），而R* 关闭步骤的数量的随机性具有可忽略不计的影响。这些结果反驳了R* 衰减步数越大，光响应越稳定的观点。我们的研究结果表明，R* 关闭是负责的光响应的可变性，而第二信使的扩散作为一个可变性抑制剂。视觉、嗅觉、味觉、激素和神经递质信号转导等生物刺激的接收和传递包含固有的可变成分。然而，生物功能是稳定和可靠的。对于每一个信号过程，它是感兴趣的调查变异性的原因和机制，通过它的变异性被减轻，以产生可靠地反映刺激的强度的反应。我们研究了视杆细胞光感受器单光子响应的变异性。一个光子被受体视紫红质捕获，它经历了一系列的生化状态，最后随机关闭。我们已经创建了这样一个过程的数学模型，基于最近的生物化学发现的激活/失活，能够再现野生型和转基因小鼠的视觉transduction的独特的实验特征。我们已经发现，视紫红质停留在这些生化状态的时间的随机性是变异性的主要原因，而携带信号的分子在细胞内的扩散作为变异性缓解。
The single photon response (SPR) in vertebrate phototransduction is regulated by the dynamics of R* during its lifetime, including the random number of phosphorylations, the catalytic activity and the random sojourn time at each phosphorylation level. Because of this randomness the electrical responses are expected to be inherently variable. However the SPR is highly reproducible. The mechanisms that confer to the SPR such a low variability are not completely understood. The kinetics of rhodopsin deactivation is investigated by a Continuous Time Markov Chain (CTMC) based on the biochemistry of rhodopsin activation and deactivation, interfaced with a spatio-temporal model of phototransduction. The model parameters are extracted from the photoresponse data of both wild type and mutant mice, having variable numbers of phosphorylation sites and, with the same set of parameters, the model reproduces both WT and mutant responses. The sources of variability are dissected into its components, by asking whether a random number of turnoff steps, a random sojourn time between steps, or both, give rise to the known variability. The model shows that only the randomness of the sojourn times in each of the phosphorylated states contributes to the Coefficient of Variation (CV) of the response, whereas the randomness of the number of R* turnoff steps has a negligible effect. These results counter the view that the larger the number of decay steps of R*, the more stable the photoresponse is. Our results indicate that R* shutoff is responsible for the variability of the photoresponse, while the diffusion of the second messengers acts as a variability suppressor. Reception and transmission of biological stimuli such as vision, olfaction, taste, and hormone and neurotransmitter signal transduction, contain inherently variable components. Yet, biological functions are stable and reliable. For each signaling process, it is of interest to investigate the causes of variability and the mechanisms by which variability is mitigated to yield responses that reliably reflect the strength of the stimulus. We have investigated the variability of the single photon response in rod photoreceptors. A photon of light is captured by a receptor rhodopsin, and it goes through a series of biochemical states ending with a random shutoff. We have created a mathematical model of such a process, based on the recent biochemical findings on activation/deactivation, capable of reproducing the peculiar experimental features of visual trasduction both in wild type and genetically modified mice. We have found that the randomness of the time that rhodopsin sojourns in each of these biochemical states is the dominant cause of variability, whereas diffusion of molecules carrying the signal within the cell acts as variability mitigators.
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DOI：
10.1523/jneurosci.0819-09.2009
发表时间：
2009-09-23
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Doan T;Azevedo AW;Hurley JB;Rieke F
通讯作者：
Rieke F
DOI：
10.1085/jgp.200308832
发表时间：
2003-10
期刊：
The Journal of general physiology
影响因子：
--
作者：
Hamer RD;Nicholas SC;Tranchina D;Liebman PA;Lamb TD
通讯作者：
Lamb TD
DOI：
10.1523/jneurosci.5391-09.2010
发表时间：
2010-03-03
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Gross OP;Burns ME
通讯作者：
Burns ME
影响因子：
5.3
作者：
Burns, ME;Mendez, A;Chen, J
通讯作者：
Chen, J
影响因子：
2.9
作者：
Gibson, SK;Parkes, JH;Liebman, PA
通讯作者：
Liebman, PA