11月24日，《美国科学院院刊》（PNAS）在线发表了中国科学院上海生命科学研究院神经科学研究所袁小兵研究组的最新研究成果—─“PKCδ Regulates Cortical Radial Migration by Stabilizing the Cdk5 Activator P35”。这项工作主要是由该研究组的赵春涛、李坤、郑望、李俊涛、梁旭俊、耿安琪、李宁等人共同完成。
细胞周期素依赖性激酶5（cyclin dependent kinase 5,Cdk5）和它的激活因子p35对大脑皮层新生神经元的放射状迁移以及分层定位发挥着至关重要的调节作用。然而，p35/Cdk5的酶活性是如何被细胞内外的信号调节的依然知之甚少。他们研究发现：新型PKC（novel PKC，nPKC）家族的一员－PKCδ可能通过维持细胞内合适的p35蛋白水平来调节大脑皮层神经元的放射状迁移。PKCδ在皮层神经元中有表达, 它可以通过直接磷酸化的方式稳定p35蛋白，延缓其降解。用胚胎宫内电场转基因技术将特异的小干扰RNA（small interference RNA，siRNA)转入神经前体细胞以降低PKCδ的表达，可严重地干扰皮层新生神经元的放射状迁移，并与降低p35的表达引起的迁移缺陷非常相似。细胞外的促迁移信号分子—─脑源性神经营养因子（brain-derived neurotrophic factor，BDNF）能够激活PKCδ，而且BDNF对Cdk5的激活需要PKCδ的参与。此外，PKCδ和p35对BDNF诱导的培养皮层神经元的迁移都是必须的。此项研究揭示了发育过程中大脑皮层神经元放射状迁移调控的新机制。
这一研究得到基金委（30625023, 30721004）、科技部（2006CB806600, 2006CB943903）和中科院（KSCX2-YW-R-103）的支持。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
推荐会议：
第一届国际医学影像和放射学新进展暨学术论著发表策略研讨会
2011 Medical Imaging and Radiological Innovations Conference
会议时间：2011年3月25日--3月27日
会议地点：上海医学院路复旦医学院明道楼
