Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago de Chile, Chile; Laboratory of Molecular Physiology and Channelopathies, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Parc de Recerca Biomédica de Barcelona, Spain.
Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago de Chile, Chile.
Biochem Biophys Res Commun. 2014 Feb 7;444(2):189-94. doi: 10.1016/j.bbrc.2014.01.031. Epub 2014 Jan 16.
Wnt signaling has a crucial role in synaptic function at the central nervous system. Here we evaluate whether Wnts affect nitric oxide (NO) generation in hippocampal neurons. We found that non-canonical Wnt-5a triggers NO production; however, Wnt-3a a canonical ligand did not exert the same effect. Co-administration of Wnt-5a with the soluble Frizzled related protein-2 (sFRP-2) a Wnt antagonist blocked the NO production. Wnt-5a activates the non-canonical Wnt/Ca(2+) signaling through a mechanism that depends on Ca(2+) release from Ryanodine-sensitive internal stores. The increase in NO levels evoked by Wnt-5a promotes the insertion of the GluN2B subunit of the NMDA receptor (NMDAR) into the neuronal cell surface. To the best of our knowledge, this is the first time that Wnt-5a signaling is related to NO production, which in turn increases NMDARs trafficking to the cell surface.
Wnt 信号在中枢神经系统的突触功能中起着至关重要的作用。在这里，我们评估 Wnts 是否会影响海马神经元中一氧化氮 (NO) 的生成。我们发现非经典 Wnt-5a 触发 NO 的产生；然而，经典配体 Wnt-3a 则没有产生同样的效果。Wnt-5a 与可溶性卷曲相关蛋白-2（sFRP-2）联合使用，sFRP-2 是一种 Wnt 拮抗剂，可阻断 NO 的产生。Wnt-5a 通过一种依赖于 Ryanodine 敏感内部储存中 Ca2+释放的机制激活非经典 Wnt/Ca2+信号。Wnt-5a 引起的 NO 水平升高促进了 NMDA 受体 (NMDAR) 的 GluN2B 亚基插入神经元细胞膜表面。据我们所知，这是 Wnt-5a 信号首次与 NO 的产生有关，而 NO 的产生又增加了 NMDAR 向细胞膜表面的转运。
