PNAS：开发出控制细胞活性和代谢过程的光控新技术

<p align="center"><img src="http://www.bioon.com/biology/UploadFiles/201208/2012081212251590.jpg" alt="" width="242" height="147" border="0" /></p>
<p align="center"><span style="font-family: 楷体_GB2312; font-size: small;">图中揭示的是细胞中脂质的形成（橘黄色），当给与蓝光时，这种脂质的形成立刻就会被催化（中间图），当蓝光关闭，这种催化效应就可以恢复（如右图）。</span></p>
近日，耶鲁大学的研究者揭示了一种光改变细胞活性的方法，其使用蓝光仅仅闪烁一毫秒就可以调节细胞内部的关键信号分子，这或许可以帮助我们调节细胞功能，来理解某些疾病的发病机制。

近几年来，一项最有创新性的研究-光遗传学或者使用遗传标记的探针来调节细胞功能对光的敏感度，这项刊登在国际著名杂志<em>PNAS</em>上的研究报告也是使用光来调节细胞膜的代谢活性。细胞的外膜是细胞与外界环境沟通的桥梁，许多细胞过程首先从细胞外膜开始进行。

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研究小组将一种对光敏感的植物蛋白与细胞膜中催化信号脂质代谢的酶类进行结合形成复合物，当这种复合物在动物细胞中进行表达的时候，科学家们可以通过蓝光来改变细胞的性质，比如细胞的形状或者其运动的能力。通过关闭蓝光，研究者也可以快速逆转这种诱导的改变，而且也可以通过蓝光照亮细胞的某些区域来调节细胞的活性。

研究者Pietro表示，这是一种强大的工具，可以精确操控细胞膜脂质的代谢以及实时研究细胞的行为。细胞膜脂质的异常代谢涉及很多疾病，包括癌症、糖尿病和神经变性等疾病。研究小组重点研究神经系统的功能，他们希望使用这种技术来操控神经元特殊部分的脂质从而来研究这种机制的破坏是如何促使疾病发生的。

相关研究由国立卫生研究院等机构支持.

编译自：<a title="" href="http://machineslikeus.com/news/light-burst-alters-cell-activity" target="_blank">Light burst alters cell activity</a>
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<a title="" href="http://dx.doi.org/doi:10.1073/pnas.1211305109" target="_blank">doi:10.1073/pnas.1211305109</a>
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<br/><strong>Optogenetic control of phosphoinositide metabolism</strong><br/>


Olof Idevall-Hagrena,b,c, Eamonn J. Dicksond, Bertil Hilled, Derek K. Toomrea, and Pietro De Camillia,b,c,1

Phosphoinositides (PIs) are lipid components of cell membranes that regulate a wide variety of cellular functions. Here we exploited the blue light-induced dimerization between two plant proteins, cryptochrome 2 (CRY2) and the transcription factor CIBN, to control plasma membrane PI levels rapidly, locally, and reversibly. The inositol 5-phosphatase domain of OCRL (5-ptaseOCRL), which acts on PI(4,5)P2 and PI(3,4,5)P3, was fused to the photolyase homology region domain of CRY2, and the CRY2-binding domain, CIBN, was fused to plasma membrane-targeting motifs. Blue-light illumination (458–488 nm) of mammalian cells expressing these constructs resulted in nearly instantaneous recruitment of 5-ptaseOCRL to the plasma membrane, where it caused rapid (within seconds) and reversible (within minutes) dephosphorylation of its targets as revealed by diverse cellular assays: dissociation of PI(4,5)P2 and PI(3,4,5)P3 biosensors, disappearance of endocytic clathrin-coated pits, nearly complete inhibition of KCNQ2/3 channel currents, and loss of membrane ruffling. Focal illumination resulted in local and transient 5-ptaseOCRL recruitment and PI(4,5)P2 dephosphorylation, causing not only local collapse and retraction of the cell edge or process but also compensatory accumulation of the PI(4,5)P2 biosensor and membrane ruffling at the opposite side of the cells. Using the same approach for the recruitment of PI3K, local PI(3,4,5)P3 synthesis and membrane ruffling could be induced, with corresponding loss of ruffling distally to the illuminated region. This technique provides a powerful tool for dissecting with high spatial–temporal kinetics the cellular functions of various PIs and reversibly controlling the functions of downstream effectors of these signaling lipids.

<br/>来源：生物谷

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