圖中揭示的是細胞中脂質(zhì)的形成（橘黃色）,，當(dāng)給與藍光時，這種脂質(zhì)的形成立刻就會被催化（中間圖）,，當(dāng)藍光關(guān)閉,，這種催化效應(yīng)就可以恢復(fù)（如右圖）。
2012年8月12日 訊 /生物谷BIOON/ --近日,，耶魯大學(xué)的研究者揭示了一種光改變細胞活性的方法,，其使用藍光僅僅閃爍一毫秒就可以調(diào)節(jié)細胞內(nèi)部的關(guān)鍵信號分子，這或許可以幫助我們調(diào)節(jié)細胞功能,，來理解某些疾病的發(fā)病機制,。
近幾年來，一項最有創(chuàng)新性的研究-光遺傳學(xué)或者使用遺傳標(biāo)記的探針來調(diào)節(jié)細胞功能對光的敏感度,，這項刊登在國際著名雜志PNAS上的研究報告也是使用光來調(diào)節(jié)細胞膜的代謝活性,。細胞的外膜是細胞與外界環(huán)境溝通的橋梁,，許多細胞過程首先從細胞外膜開始進行。
研究小組將一種對光敏感的植物蛋白與細胞膜中催化信號脂質(zhì)代謝的酶類進行結(jié)合形成復(fù)合物,，當(dāng)這種復(fù)合物在動物細胞中進行表達的時候,，科學(xué)家們可以通過藍光來改變細胞的性質(zhì)，比如細胞的形狀或者其運動的能力,。通過關(guān)閉藍光,，研究者也可以快速逆轉(zhuǎn)這種誘導(dǎo)的改變，而且也可以通過藍光照亮細胞的某些區(qū)域來調(diào)節(jié)細胞的活性,。
研究者Pietro表示,，這是一種強大的工具，可以精確操控細胞膜脂質(zhì)的代謝以及實時研究細胞的行為,。細胞膜脂質(zhì)的異常代謝涉及很多疾病,，包括癌癥、糖尿病和神經(jīng)變性等疾病,。研究小組重點研究神經(jīng)系統(tǒng)的功能,，他們希望使用這種技術(shù)來操控神經(jīng)元特殊部分的脂質(zhì)從而來研究這種機制的破壞是如何促使疾病發(fā)生的。
相關(guān)研究由國立衛(wèi)生研究院等機構(gòu)支持,。（生物谷Bioon.com）
編譯自：Light burst alters cell activity
doi:10.1073/pnas.1211305109
PMC:
PMID:
Optogenetic control of phosphoinositide metabolism
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.
