nuclear calcium signaling controls expression of a large gene pool identification of a gene program for acquired neuroprotection induced by synaptic activity核钙信号控制一个大基因库的表达基因的识别项目获得神经保护引起的突触活动.pdfVIP

Nuclear Calcium Signaling Controls Expression of a Large Gene Pool: Identification of a Gene Program for Acquired Neuroprotection Induced by Synaptic Activity 1¤a 1¤b 1¤a 1 ´ ´ 1 2 Sheng-Jia Zhang , Ming Zou , Li Lu , David Lau , Desiree A. W. Ditzel , Celine Delucinge-Vivier , 1¤c 2 1 Yoshinori Aso , Patrick Descombes , Hilmar Bading * ´ 1 Department of Neurobiology, Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg, Heidelberg, Germany, 2 Genomics Platform, Centre Medical ´ ` Universitaire, Universite de Geneve, Geneva, Switzerland Abstract Synaptic activity can boost neuroprotection through a mechanism that requires synapse-to-nucleus communication and calcium signals in the cell nucleus. Here we show that in hippocampal neurons nuclear calcium is one of the most potent signals in neuronal gene expression. The induction or repression of 185 neuronal activity-regulated genes is dependent upon nuclear calcium signaling. The nuclear calcium-regulated gene pool contains a genomic program that mediates synaptic activity-induced, acquired neuroprotection. The core set of neuroprotective genes consists of 9 principal components, termed Activity-regulated Inhibitor of Death (AID) genes, and includes Atf3, Btg2, GADD45b, GADD45c, Inhibin b- A, Interferon activated gene 202B, Npas4, Nr4a1, and Serpinb2, which strongly promote sur