SynGAP regulates protein synthesis and homeostatic synaptic plasticity in developing cortical networks.
SynGAP regulates protein synthesis and homeostatic synaptic plasticity in developing cortical networks.
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DOI：
10.1371/journal.pone.0083941
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hall BJ
中科院分区：
文献类型：
--
作者：
Wang CC;Held RG;Hall BJ
在发育中的大脑中，破坏兴奋性和抑制性神经传递之间的平衡与智力残疾（ID）和自闭症谱系障碍（ASD）有因果关系。兴奋性突触强度在中枢神经系统中通过控制突触后α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPARs）的数量来调节。突触gtpase激活蛋白（SynGAP）的新生基因突变与ID和ASD有关。SynGAP在兴奋性突触富集，基因抑制SynGAP可增加兴奋性突触强度。然而，SynGAP究竟是如何维持突触AMPAR含量的尚不清楚。我们在这里表明SynGAP限制兴奋性突触强度，部分是通过抑制皮质神经元中的蛋白质合成。来自体外、大鼠和小鼠皮质网络的数据表明，SynGAP对翻译的调控涉及ERK、mTOR和小gtp结合蛋白Rheb。此外，这些数据表明，含有glun2b的NMDARs和认知激酶CaMKII作用于SynGAP的上游，这一信号级联是发育皮层网络中兴奋性突触适当的翻译依赖的稳态突触可塑性所必需的。
Disrupting the balance between excitatory and inhibitory neurotransmission in the developing brain has been causally linked with intellectual disability (ID) and autism spectrum disorders (ASD). Excitatory synapse strength is regulated in the central nervous system by controlling the number of postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). De novo genetic mutations of the synaptic GTPase-activating protein (SynGAP) are associated with ID and ASD. SynGAP is enriched at excitatory synapses and genetic suppression of SynGAP increases excitatory synaptic strength. However, exactly how SynGAP acts to maintain synaptic AMPAR content is unclear. We show here that SynGAP limits excitatory synaptic strength, in part, by suppressing protein synthesis in cortical neurons. The data presented here from in vitro, rat and mouse cortical networks, demonstrate that regulation of translation by SynGAP involves ERK, mTOR, and the small GTP-binding protein Rheb. Furthermore, these data show that GluN2B-containing NMDARs and the cognitive kinase CaMKII act upstream of SynGAP and that this signaling cascade is required for proper translation-dependent homeostatic synaptic plasticity of excitatory synapses in developing cortical networks.
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DOI：
10.1523/jneurosci.4022-09.2010
发表时间：
2010-02-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Foster KA;McLaughlin N;Edbauer D;Phillips M;Bolton A;Constantine-Paton M;Sheng M
通讯作者：
Sheng M
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
16.2
作者：
Gray JA;Shi Y;Usui H;During MJ;Sakimura K;Nicoll RA
通讯作者：
Nicoll RA
影响因子：
4.8
作者：
Fonseca, Bruno D.;Alain, Tommy;Proud, Christopher G.
通讯作者：
Proud, Christopher G.
影响因子：
2.5
作者：
Chen, HX;Roper, SN
通讯作者：
Roper, SN