TORC1 controls the kinetics of CRE-target gene transcription and dendritic growth of developing cortical neurons

作     者：Shuai LI,Yang ZHOU,Zhi-Qi XIONG Institute of Neuroscience and Key Laboratory of Neurobiology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China 

会议名称：《中国神经科学学会第四次会员代表大会暨第七届全国学术会议》

会议日期：2007年

学科分类：0710[理学-生物学] 07[理学] 071006[理学-神经生物学] 

关 键 词：CREB TORC1 dendrite arborization 

摘      要：正Activity-dependent CREB-target gene transcription is implicated in cortical dendritic ***, the molecular mechanisms regulating CREB-target gene transcription and dendritic morphogenesis are not well understood. We here reported that the CREB coacti vator TORC 1（transducer of regulated CREB 1） controls the kinetics of CREB-target gene transcription and dendritic ***1 is highly expressed in the developing ***～（2+） influx induced persistent CREB phosphorylation,but transient CRE-target gene transcription in cultured developing cortical neurons. The kinetics of CREB-target gene transcription paralleled that of the nuclear translocation of ***-dependent nuclear translocation of TORC 1 activated the transcription of CREB-target genes,including salt-inducible kinase 1（SIK1）. SIK1 could phosphorylate TORC1 and then terminated TORC1-mediated CRE-target gene transcription by driving the nuclear exportation of ***,overexpressing a wild-type form of TORC1 promoted activity-dependent dendritic growth,an effect was further potentiated by down-regulating *** expressing a dominant-negative form, knocking down TORC1,or overexpressing SIK1 blocked activity-dependent dendritic *** observations identify TORC1 as a molecular switch of neuronal activity-dependent CREB target gene transcription and dendritic development.