MEF2转录因子的活性依赖性调节抑制兴奋性突触数量。

Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number.

作者信息

Flavell Steven W, Cowan Christopher W, Kim Tae-Kyung, Greer Paul L, Lin Yingxi, Paradis Suzanne, Griffith Eric C, Hu Linda S, Chen Chinfei, Greenberg Michael E

机构信息

Neurobiology Program, Children's Hospital, and Departments of Neurology and Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.

出版信息

Science. 2006 Feb 17;311(5763):1008-12. doi: 10.1126/science.1122511.

DOI:10.1126/science.1122511

PMID:16484497

Abstract

In the mammalian nervous system, neuronal activity regulates the strength and number of synapses formed. The genetic program that coordinates this process is poorly understood. We show that myocyte enhancer factor 2 (MEF2) transcription factors suppressed excitatory synapse number in a neuronal activity- and calcineurin-dependent manner as hippocampal neurons formed synapses. In response to increased neuronal activity, calcium influx into neurons induced the activation of the calcium/calmodulin-regulated phosphatase calcineurin, which dephosphorylated and activated MEF2. When activated, MEF2 promoted the transcription of a set of genes, including arc and synGAP, that restrict synapse number. These findings define an activity-dependent transcriptional program that may control synapse number during development.

摘要

在哺乳动物神经系统中，神经元活动调节所形成突触的强度和数量。协调这一过程的基因程序目前还知之甚少。我们发现，当海马神经元形成突触时，肌细胞增强因子2（MEF2）转录因子以神经元活动和钙调神经磷酸酶依赖的方式抑制兴奋性突触的数量。随着神经元活动增加，钙离子流入神经元会诱导钙/钙调蛋白调节的磷酸酶钙调神经磷酸酶的激活，后者使MEF2去磷酸化并激活。激活后，MEF2促进包括arc和synGAP在内的一组限制突触数量的基因的转录。这些发现确定了一种活动依赖的转录程序，该程序可能在发育过程中控制突触数量。