Kurisaki A, Inoue I, Kurisaki K, Yamakawa N, Tsuchida K, Sugino H
Institute for Enzyme Research, The University of Tokushima, Kuramoto, Tokushima 770-8503, Japan.
Neuroscience. 2008 Feb 19;151(4):1225-35. doi: 10.1016/j.neuroscience.2007.12.012. Epub 2007 Dec 15.
Calcium entry into the postsynaptic neuron through N-methyl-D-aspartate-type glutamate receptors (NMDARs) triggers the induction of long-term potentiation (LTP), which is considered to contribute to synaptic plasticity and plays a critical role in behavioral learning. We report here that activin, a member of the transforming growth factor-beta (TGF-beta) superfamily, promotes phosphorylation of NMDARs and increases the Ca2+ influx through these receptors in primary cultured rat hippocampal neurons. This signal transduction occurs in a functional complex of activin receptors, NMDARs, and Src family tyrosine kinases, including Fyn, formed on a multimer of postsynaptic scaffolding postsynaptic density protein 95/Dlg/ZO-1 (PDZ), activin receptor interacting protein 1 (ARIP1). Activin-induced NMDAR activation persists for more than 24 h, which is complimentary to the activation time of NMDARs by brain-derived neurotrophic factor (BDNF). Our results suggest that activin is a unique and powerful potentiator for NMDAR-dependent signaling, which could be involved in the regulatory mechanisms of synaptic plasticity.
钙离子通过N-甲基-D-天冬氨酸型谷氨酸受体（NMDARs）进入突触后神经元，触发长时程增强（LTP）的诱导，LTP被认为有助于突触可塑性，并在行为学习中起关键作用。我们在此报告，激活素是转化生长因子-β（TGF-β）超家族的成员，它能促进NMDARs的磷酸化，并增加原代培养的大鼠海马神经元中通过这些受体的Ca2+内流。这种信号转导发生在由激活素受体、NMDARs和Src家族酪氨酸激酶（包括Fyn）组成的功能复合物中，该复合物形成于突触后支架突触后致密蛋白95/Dlg/ZO-1（PDZ）、激活素受体相互作用蛋白1（ARIP1）的多聚体上。激活素诱导的NMDAR激活持续超过24小时，这与脑源性神经营养因子（BDNF）对NMDARs的激活时间互补。我们的结果表明，激活素是NMDAR依赖性信号传导的一种独特而强大的增强剂，可能参与突触可塑性的调节机制。
