Regulation of NMDA-receptor synaptic transmission by Wnt signaling.
Regulation of NMDA-receptor synaptic transmission by Wnt signaling.
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DOI：
10.1523/jneurosci.6311-10.2011
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发表时间：
2011-06-29
期刊：
影响因子：
--
通讯作者：
Barria A
中科院分区：
文献类型：
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作者：
Cerpa W;Gambrill A;Inestrosa NC;Barria A
Wnt配体是一种分泌型糖蛋白，控制神经系统胚胎发育过程中的基因表达和细胞骨架重组。然而，它们在大脑发育后期的作用，特别是在已建立的突触连接的调节中的作用尚不清楚。我们发现，Wnt-5a急性和特异性上调突触NMDAR电流在大鼠海马切片促进诱导LTP，学习和记忆的细胞模型。这种效应需要增加突触后Ca 2+和激活Wnt信号通路的非经典下游效应子。相反，经典Wnt信号通路的激活剂Wnt-7a对NMDAR介导的突触传递没有影响。此外，内源性Wnt配体是维持基础NMDAR突触传递调节突触增强阈值所必需的。Wnt配体的这种新作用为Wnt信号传导提供了一种机制，以在发育后期和成熟生物体中急性调节突触可塑性和脑功能。
Wnt ligands are secreted glycoproteins controlling gene expression and cytoskeleton reorganization involved in embryonic development of the nervous system. However, their role in later stages of brain development, particularly in the regulation of established synaptic connections is not known. We found that Wnt-5a acutely and specifically up-regulates synaptic NMDAR currents in rat hippocampal slices facilitating induction of LTP, a cellular model of learning and memory. This effect requires an increase in postsynaptic Ca2+ and activation of non-canonical downstream effectors of the Wnt signaling pathway. In contrast, Wnt-7a, an activator of the canonical Wnt signaling pathway, has no effect on NMDAR mediated synaptic transmission. Moreover, endogenous Wnt ligands are necessary to maintain basal NMDAR synaptic transmission adjusting the threshold for synaptic potentiation. This novel role for Wnt ligands provides a mechanism for Wnt signaling to acutely modulate synaptic plasticity and brain function in later stages of development and in the mature organism.