美國圣朱迪兒童研究醫(yī)院的研究人員發(fā)現(xiàn)了控制大腦神經(jīng)細(xì)胞遷移的新機(jī)制,。這不僅有助于了解胎兒和嬰幼兒時(shí)期人類大腦的發(fā)育情況,，還有助于對兒童癲癇,、智障以及腦腫瘤轉(zhuǎn)移有更新的認(rèn)識,，具有十分重要的臨床意義,。近期出版的《神經(jīng)元》刊登了相關(guān)研究成果,。
在大腦的發(fā)育過程中,，神經(jīng)細(xì)胞往往產(chǎn)生于遠(yuǎn)離其最終發(fā)揮作用位點(diǎn)的萌發(fā)區(qū)域,，因此需要遷移到最終位點(diǎn)，才能整合到大腦的“電路”之中,，發(fā)揮其功能作用,。研究表明，神經(jīng)細(xì)胞會(huì)沿著神經(jīng)膠質(zhì)細(xì)胞產(chǎn)生的纖維移動(dòng),；一種叫Par6α的控制分子會(huì)調(diào)節(jié)這種遷移,，而一種被稱為肌球蛋白Ⅱ的分子馬達(dá)則會(huì)為這種遷移提供動(dòng)力。
研究人員使用了顯微鏡延時(shí)成像技術(shù),，來確定肌球蛋白Ⅱ和肌動(dòng)蛋白在神經(jīng)細(xì)胞遷移過程中的機(jī)械原理,。他們培養(yǎng)出處于遷移狀態(tài)的神經(jīng)細(xì)胞，用熒光染料來標(biāo)注肌球蛋白Ⅱ,、肌動(dòng)蛋白和關(guān)鍵的神經(jīng)細(xì)胞結(jié)構(gòu),；之后利用激光速射脈沖對培養(yǎng)細(xì)胞進(jìn)行拍照，每次閃光都會(huì)拍出一張顯微照片,。這樣做的結(jié)果是得到一系列“微電影”,，這些“微電影”演示了促使神經(jīng)細(xì)胞遷移的肌球蛋白Ⅱ—肌動(dòng)蛋白機(jī)制。肌球蛋白Ⅱ—肌動(dòng)蛋白機(jī)制會(huì)把神經(jīng)細(xì)胞的內(nèi)部細(xì)胞構(gòu)建物向前拉扯,，這些細(xì)胞構(gòu)建物會(huì)架設(shè)“腳手架”,，以使神經(jīng)細(xì)胞將主要的細(xì)胞體向前移動(dòng)。研究人員證明,，在這一過程中,，肌球蛋白Ⅱ和肌動(dòng)蛋白都是必需的，一旦使用了分子抑制藥物,，它們就會(huì)完全中斷遷移過程,；此外，他們還發(fā)現(xiàn),，在神經(jīng)細(xì)胞頂部區(qū)域,，肌球蛋白Ⅱ的收縮會(huì)為神經(jīng)細(xì)胞的移動(dòng)提供動(dòng)力。（生物谷Bioon.com）
生物谷推薦原始出處：
Neuron, Volume 63, Issue 1, 63-80, 16 July 2009 doi:10.1016/j.neuron.2009.05.028
Myosin II Motors and F-Actin Dynamics Drive the Coordinated Movement of the Centrosome and Soma during CNS Glial-Guided Neuronal Migration
David J. Solecki1,,,Niraj Trivedi1,Eve-Ellen Govek2,Ryan A. Kerekes3,Shaun S. Gleason3andMary E. Hatten2
1 Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA
2 Laboratory of Developmental Neurobiology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA
3 Image Science and Machine Vision Group, Measurement Science and Systems Engineering Division, Oak Ridge National Laboratory, 1 Bethel Valley Road, Oak Ridge, TN 37830, USA
Lamination of cortical regions of the vertebrate brain depends on glial-guided neuronal migration. The conserved polarity protein Par6α localizes to the centrosome and coordinates forward movement of the centrosome and soma in migrating neurons. The cytoskeletal components that produce this unique form of cell polarity and their relationship to polarity signaling cascades are unknown. We show that F-actin and Myosin II motors are enriched inthe neuronal leading process and that Myosin II activity is necessary for leading process actin dynamics. Inhibition of Myosin II decreased the speed of centrosome and somal movement, whereas Myosin II activation increased coordinated movement. Ectopic expression or silencing of Par6 inhibited Myosin II motors by decreasing Myosin light-chain phosphorylation. These findings suggest leading-process Myosin II may function to pull the centrosomeand soma forward during glial-guided migration bya mechanism involving the conserved polarity protein Par6α.
