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首页> 外文期刊>Journal of Computational Neuroscience >Spatiotemporal maps of CaMKII in dendritic spines
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Spatiotemporal maps of CaMKII in dendritic spines

机译：CaMKII在树突棘中的时空图

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摘要

The calcium calmodulin dependent kinase (CaMKII) is important for long-term potentiation at dendritic spines. Photo-activatable GFP (PaGFP) - CaMKII fusions were used to map CaMKII movements between and within spines in dissociated hippocampal neurons. Photo-activated PaGFP (GFP*) generated in the shaft spread uniformly, but was retained for about 1 s in spines. The differential localization of GFP*-CaMKII isoforms was visualized with hundred nanometer precision frame to frame using de-noising algorithms. GFP*-CaMKIIα localized to the tips of mushroom spines. The spatiotemporal profiles of native and kinase defective GFP*-CaMKIIβ, differed markedly from GFP*-CaMKIIα and mutant GFP*-CaMKIIβ lacking the association domain. CaMKII β bound to cortical actin in the dendrite and the stable actin network in spine bodies. Glu-tamate produced a transiently localized GFP*-CaMKIIα fraction and a soluble GFP*-CaMKII|3 fraction in spine bodies. Single molecule simulations of the interplay between diffusion and biochemistry of GFP* species were guided by the spatiotemporal maps and set limits on binding parameters. They highlighted the role of spine morphology in modulating bound CaMKII lifetimes. The long residence times of GFP*-CaMKIIβ relative to GFP*-CaMKIIα followed as consequence of more binding sites on the actin cytoskeleton than the post-synaptic density. These factors combined to retain CaMKII for tens of seconds, sufficient to outlast the calcium transients triggered by glutamate, without invoking complex biochemistry.
机译：钙调蛋白依赖性激酶（CaMKII）对于树突棘的长期增强很重要。光激活GFP（PaGFP）-CaMKII融合体被用来绘制CaMKII在解离的海马神经元棘之间和内部的运动。杆身中产生的光活化PaGFP（GFP *）均匀分布，但在棘中保留约1 s。 GFP * -CaMKII同工型的差异化定位使用去噪算法以百纳米精度的帧对帧可视化。 GFP *-CaMKIIα位于蘑菇棘的顶端。天然和激酶缺陷的GFP *-CaMKIIβ的时空分布与缺少关联域的GFP *-CaMKIIα和突变的GFP *-CaMKIIβ明显不同。 CaMKIIβ结合到树突中的皮质肌动蛋白和脊柱体内的稳定肌动蛋白网络。谷氨酸在脊柱体中产生一个瞬时定位的GFP *-CaMKIIα级分和一个可溶性GFP * -CaMKII | 3级分。 GFP *物种的扩散与生物化学之间相互作用的单分子模拟由时空图指导，并为结合参数设定了限制。他们强调了脊柱形态在调节结合的CaMKII寿命中的作用。 GFP *-CaMKIIβ相对于GFP *-CaMKIIα的长停留时间是肌动蛋白细胞骨架上结合位点多于突触后密度的结果。这些因素合在一起可将CaMKII保留数十秒，足以使由谷氨酸触发的钙瞬变持久，而无需进行复杂的生物化学反应。

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  • 来源
    《Journal of Computational Neuroscience》 |2012年第1期|p.123-139|共17页
  • 作者

    Shahid Khan; Thomas S. Reese; Nasir Rajpoot; Ayisha Shabbir;

  • 作者单位

    Laboratory of Neurobiology, National Institute of Neurological Disorders & Stroke, National Institutes of Health,Bethesda, MD 20892, USA,Molecular Biology Consortium,Chicago, IL 60612, USA,LUMS-School of Science & Engineering, Sector U, DHA,Lahore, Pakistan;

    Laboratory of Neurobiology, National Institute of Neurological Disorders & Stroke, National Institutes of Health,Bethesda, MD 20892, USA;

    Department of Computer Science, University of Warwick,Coventry CV4 7AL, UK,LUMS-School of Science & Engineering, Sector U, DHA,Lahore, Pakistan;

    LUMS-School of Science & Engineering, Sector U, DHA,Lahore, Pakistan;

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  • 正文语种 eng
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  • 关键词

    smoldyn; actin cytoskeleton; photoactivation; multi-color confocal microscopy; wavelet transform; cultured hippocampal neurons;

    机译：smoldyn;肌动蛋白细胞骨架光活化多色共聚焦显微镜小波变换培养的海马神经元;

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