在探索更好的癌症治疗方法过程中，科学家遇到的一个最大挑战就是首先要深入理解癌细胞转移扩散的原因和机制。最新的研究发现了细胞蛋白在分子水平活性机制。
科研人员已经开发了一项新技术，这项技术能够使用光在精确的时间控制蛋白的活性，将其放入细胞中可以控制细胞的移动。这为蛋白质功能研究提供了一种新的工具。这项研究结果发布在2009年8月19日出版的Nature杂志上。
这项技术在基础研究领域已经有了成功的应用，同样的蛋白可以导致癌症或抑制癌症，这取决于在细胞中的某些位置蛋白质是否有活性。现在，研究人员已经可以控制移动发生的位置，因此使得细胞控制技术达到了一个新的水平。
研究人员表示，这项新技术的应用使得我们初步了解了细胞的移动。我们还可将其用于控制细胞的移动方向，这将有助于胚胎发育，神经再生和癌症转移的研究。(生物谷Bioon.com)
生物谷推荐原始出处：
Nature doi:10.1038/nature08241
A genetically encoded photoactivatable Rac controls the motility of living cells
Yi I. Wu1,3, Daniel Frey4, Oana I. Lungu1,2,3, Angelika Jaehrig1,3, Ilme Schlichting4, Brian Kuhlman2,3 & Klaus M. Hahn1,3
1.Department of Pharmacology,
2.Department of Biochemistry and Biophysics, and,
3.Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA
4.Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Jahn-Strasse 29, 69120 Heidelberg, Germany
The precise spatio-temporal dynamics of protein activity are often critical in determining cell behaviour, yet for most proteins they remain poorly understood; it remains difficult to manipulate protein activity at precise times and places within living cells. Protein activity has been controlled by light, through protein derivatization with photocleavable moieties or using photoreactive small-molecule ligands. However, this requires use of toxic ultraviolet wavelengths, activation is irreversible, and/or cell loading is accomplished via disruption of the cell membrane (for example, through microinjection). Here we have developed a new approach to produce genetically encoded photoactivatable derivatives of Rac1, a key GTPase regulating actin cytoskeletal dynamics in metazoan cells. Rac1 mutants were fused to the photoreactive LOV (light oxygen voltage) domain from phototropin, sterically blocking Rac1 interactions until irradiation unwound a helix linking LOV to Rac1. Photoactivatable Rac1 (PA-Rac1) could be reversibly and repeatedly activated using 458- or 473-nm light to generate precisely localized cell protrusions and ruffling. Localized Rac activation or inactivation was sufficient to produce cell motility and control the direction of cell movement. Myosin was involved in Rac control of directionality but not in Rac-induced protrusion, whereas PAK was required for Rac-induced protrusion. PA-Rac1 was used to elucidate Rac regulation of RhoA in cell motility. Rac and Rho coordinate cytoskeletal behaviours with seconds and submicrometre precision. Their mutual regulation remains controversial, with data indicating that Rac inhibits and/or activates Rho. Rac was shown to inhibit RhoA in mouse embryonic fibroblasts, with inhibition modulated at protrusions and ruffles. A PA-Rac crystal structure and modelling revealed LOV–Rac interactions that will facilitate extension of this photoactivation approach to other proteins.
