The nogo receptor family restricts synapse number in the developing hippocampus.

The nogo receptor family restricts synapse number in the developing hippocampus.
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DOI:
10.1016/j.neuron.2011.11.029
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发表时间:
2012-02-09
期刊:
影响因子:
16.2
通讯作者:
Greenberg ME
Greenberg ME
中科院分区:
医学1区
文献类型:
--
作者:
Wills ZP;Mandel-Brehm C;Mardinly AR;McCord AE;Giger RJ;Greenberg ME

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神经元发育的特征是突触旺盛生长的时期,这一点得到了很好的研究。然而,限制这一过程的机制还不太清楚。在这里,我们证明了Nogo受体家族的糖基磷脂酰肌醇锚定的细胞表面受体(NgR1、NgR2和NgR3)限制兴奋性突触的形成。在体外,任何一个NGRs的缺失都会导致突触数量的增加,而在体内,这三个受体的缺失是异常升高的突触发生所必需的。我们发现,NGR1通过共同受体Troy和RhoA发出信号,抑制突触后神经元中新突触的形成。NGR家族受到神经元活动的下调,这种反应可能会限制NGR的功能,并促进活动依赖型突触的发育。这些发现表明,NgR1,一种先前被证明限制成人轴突生长的受体,也在树突中作为屏障发挥作用,在大脑发育过程中限制兴奋性突触的数量。
Neuronal development is characterized by a period of exuberant synaptic growth that is well studied. However, the mechanisms that restrict this process are less clear. Here we demonstrate that glycosyl-phosphatidylinositol-anchored cell-surface receptors of the Nogo Receptor family (NgR1, NgR2, and NgR3) restrict excitatory synapse formation. Loss of any one of the NgRs results in an increase in synapse number in vitro, whereas loss of all three is necessary for abnormally elevated synaptogenesis in vivo. We show that NgR1 inhibits the formation of new synapses in the postsynaptic neuron by signaling through the coreceptor TROY and RhoA. The NgR family is downregulated by neuronal activity, a response that may limit NgR function and facilitate activity-dependent synapse development. These findings suggest that NgR1, a receptor previously shown to restrict axon growth in the adult, also functions in the dendrite as a barrier that limits excitatory synapse number during brain development.
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