11月24日,，《美國科學(xué)院院刊》（PNAS）在線發(fā)表了中國科學(xué)院上海生命科學(xué)研究院神經(jīng)科學(xué)研究所袁小兵研究組的最新研究成果—─“PKCδ Regulates Cortical Radial Migration by Stabilizing the Cdk5 Activator P35”。這項(xiàng)工作主要是由該研究組的趙春濤,、李坤,、鄭望,、李俊濤、梁旭俊,、耿安琪,、李寧等人共同完成。
細(xì)胞周期素依賴性激酶5（cyclin dependent kinase 5,Cdk5）和它的激活因子p35對(duì)大腦皮層新生神經(jīng)元的放射狀遷移以及分層定位發(fā)揮著至關(guān)重要的調(diào)節(jié)作用,。然而,，p35/Cdk5的酶活性是如何被細(xì)胞內(nèi)外的信號(hào)調(diào)節(jié)的依然知之甚少。他們研究發(fā)現(xiàn)：新型PKC（novel PKC,，nPKC）家族的一員－PKCδ可能通過維持細(xì)胞內(nèi)合適的p35蛋白水平來調(diào)節(jié)大腦皮層神經(jīng)元的放射狀遷移,。PKCδ在皮層神經(jīng)元中有表達(dá), 它可以通過直接磷酸化的方式穩(wěn)定p35蛋白，延緩其降解,。用胚胎宮內(nèi)電場(chǎng)轉(zhuǎn)基因技術(shù)將特異的小干擾RNA（small interference RNA,，siRNA)轉(zhuǎn)入神經(jīng)前體細(xì)胞以降低PKCδ的表達(dá)，可嚴(yán)重地干擾皮層新生神經(jīng)元的放射狀遷移,，并與降低p35的表達(dá)引起的遷移缺陷非常相似,。細(xì)胞外的促遷移信號(hào)分子—─腦源性神經(jīng)營養(yǎng)因子（brain-derived neurotrophic factor，BDNF）能夠激活PKCδ,，而且BDNF對(duì)Cdk5的激活需要PKCδ的參與,。此外，PKCδ和p35對(duì)BDNF誘導(dǎo)的培養(yǎng)皮層神經(jīng)元的遷移都是必須的,。此項(xiàng)研究揭示了發(fā)育過程中大腦皮層神經(jīng)元放射狀遷移調(diào)控的新機(jī)制,。
這一研究得到基金委（30625023, 30721004）、科技部（2006CB806600, 2006CB943903）和中科院（KSCX2-YW-R-103）的支持,。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS November 24, 2009, doi: 10.1073/pnas.0812872106
PKCδ regulates cortical radial migration by stabilizing the Cdk5 activator p35
Chun-tao Zhaoa,b, Kun Lia,b, Jun-tao Lia,b, Wang Zhenga,b, Xu-jun Lianga,b, An-qi Genga, Ning Lia,b and Xiao-bing Yuana,1
aInstitute of Neuroscience and State Key Laboratory of Neurobiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; and
bGraduate School of the Chinese Academy of Sciences, Shanghai 200031, China
Cyclin-dependent kinase 5 (Cdk5) and its activator p35 are critical for radial migration and lamination of cortical neurons. However, how this kinase is regulated by extracellular and intracellular signals during cortical morphogenesis remains unclear. Here, we show that PKCδ, a member of novel PKC expressing in cortical neurons, could stabilize p35 by direct phosphorylation. PKCδ attenuated the degradation of p35 but not its mutant derivative, which could not be phosphorylated by PKCδ. Down-regulation of PKCδ by in utero electroporation of specific small interference RNA (siRNA) severely impaired the radial migration of cortical neurons. This migration defect was similar to that caused by down-regulation of p35 and could be prevented by cotransfection with the wild-type but not the mutant p35. Furthermore, PKCδ could be activated by the promigratory factor brain-derived neurotrophic factor (BDNF) and was required for the activation of Cdk5 by BDNF. Both PKCδ and p35 were required for the promigratory effect of BDNF on cultured newborn neurons. Thus, PKCδ may promote cortical radial migration through maintaining the proper level of p35 in newborn neurons.
推薦會(huì)議：
第一屆國際醫(yī)學(xué)影像和放射學(xué)新進(jìn)展暨學(xué)術(shù)論著發(fā)表策略研討會(huì)
2011 Medical Imaging and Radiological Innovations Conference
會(huì)議時(shí)間：2011年3月25日--3月27日
會(huì)議地點(diǎn)：上海醫(yī)學(xué)院路復(fù)旦醫(yī)學(xué)院明道樓
