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Title: TORC1 Regulates Activity-Dependent CREB-Target Gene Transcription and Dendritic Growth of Developing Cortical Neurons
Author: Li, Shuai ; Zhang, Chi ; Takemori, Hiroshi ; Zhou, Yang ; null(熊志奇)
Source: JOURNAL OF NEUROSCIENCE
Issued Date: 2009
Volume: 29, Issue:8, Pages:2334-2343
Keyword: activity ; CREB ; dendritic arborization ; gene ; transcription ; development ; CAM-KINASE-IV ; SENSITIVE COINCIDENCE DETECTOR ; CALCIUM REGULATION ; COACTIVATOR TORC2 ; IN-VIVO ; PHOSPHORYLATION ; ACTIVATION ; EXPRESSION ; MECHANISM ; SIGNALS
Subject: Neurosciences & Neurology
Corresponding Author: Zhou, Y (reprint author), Chinese Acad Sci, Inst Neurosci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China,yzhou@ion.ac.cn ; xiongzhiqi@ion.ac.cn
English Abstract: CREB-target gene transcription during neuronal excitation is important for many aspects of neuronal development and function, including dendrite morphogenesis. However, the signaling events that regulate cAMP response element-binding protein (CREB)-mediated gene transcription during dendritic development are not well understood. Herein we report that the CREB coactivator TORC1 (transducer of regulated CREB 1) is required for activity-dependent CREB-target gene expression and dendrite growth in developing cortical neurons. Ca(2+) influx via voltage-gated calcium channels induced TORC1 dephosphorylation and translocation into the nucleus in a calcineurin-dependent manner. Nuclear accumulation of TORC1 initiated the expression of CREB-target genes, including salt-inducible kinase 1 (SIK1). In response of persistent depolarization, de novo SIK1 protein in turn promoted TORC1 phosphorylation and consequent depletion of nucleus-localized TORC1. SIK1 induction thus appears to act as a negative feedback signal that prevents persistent CREB/TORC1-dependent transcription in the face of long-lasting neuronal activity. Overexpressing wild type TORC1 promoted basal as well as activity-induced dendritic growth, whereas expressing a dominant-negative form of TORC1 or downregulating TORC1 inhibited activity-dependent dendritic growth in vitro and in vivo. Together, these results suggest that neuronal activity-dependent dendritic growth in developing cortical neurons relies on transient TORC1-mediated CREB-target gene transcription.
Indexed Type: sci
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1676
Appears in Collections:神经所(总)_期刊论文
疾病神经生物学研究组_期刊论文

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Li, Shuai; Zhang, Chi; Takemori, Hiroshi; Zhou, Yang; Xiong, Zhi-Qi.TORC1 Regulates Activity-Dependent CREB-Target Gene Transcription and Dendritic Growth of Developing Cortical Neurons,JOURNAL OF NEUROSCIENCE,2009,29(8):2334-2343
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