在探索更好的癌癥治療方法過程中,，科學家遇到的一個最大挑戰(zhàn)就是首先要深入理解癌細胞轉(zhuǎn)移擴散的原因和機制,。最新的研究發(fā)現(xiàn)了細胞蛋白在分子水平活性機制。
科研人員已經(jīng)開發(fā)了一項新技術(shù),，這項技術(shù)能夠使用光在精確的時間控制蛋白的活性,，將其放入細胞中可以控制細胞的移動。這為蛋白質(zhì)功能研究提供了一種新的工具,。這項研究結(jié)果發(fā)布在2009年8月19日出版的Nature雜志上,。
這項技術(shù)在基礎(chǔ)研究領(lǐng)域已經(jīng)有了成功的應(yīng)用，同樣的蛋白可以導致癌癥或抑制癌癥,，這取決于在細胞中的某些位置蛋白質(zhì)是否有活性?，F(xiàn)在，研究人員已經(jīng)可以控制移動發(fā)生的位置,，因此使得細胞控制技術(shù)達到了一個新的水平,。
研究人員表示，這項新技術(shù)的應(yīng)用使得我們初步了解了細胞的移動,。我們還可將其用于控制細胞的移動方向,，這將有助于胚胎發(fā)育，神經(jīng)再生和癌癥轉(zhuǎn)移的研究,。(生物谷Bioon.com)
生物谷推薦原始出處：
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.
