Ca2+-dependent binding of calcium-binding protein 1 to presynaptic group III metabotropic glutamate receptors and blockage by phosphorylation of the receptors.
Ca2+-dependent binding of calcium-binding protein 1 to presynaptic group III metabotropic glutamate receptors and blockage by phosphorylation of the receptors.
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钙结合蛋白 1 与突触前 III 族代谢型谷氨酸受体的 Ca2 依赖性结合，并通过受体磷酸化进行阻断。
DOI：
10.1016/j.bbrc.2011.08.006
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Yoshiaki Nakajima
中科院分区：
文献类型：
--
作者：
市原和明;内原俊記;中村綾子;鈴木良夫;水谷智彦;内原俊記;Nakajima Y;Yoshiaki Nakajima
突触前III组代谢谷氨酸受体（mGluRs）和Ca2+通道是突触囊泡释放的主要神经元活动依赖性调节因子，它们在信号级联中使用共同分子。其中，钙调蛋白（CaM）和相关的EF-hand Ca2+结合蛋白作为突触前Ca2+的传感器是特别重要的，它们中的许多确实在Ca2+通道的信号传导中被利用。然而，尽管其结构保守，CaM是唯一已知的EF-hand Ca2+结合蛋白，用于突触前III组mGluRs的信号传导。由于mGluRs和Ca2+通道相互调节，并在功能上收敛于突触囊泡释放的调节，因此mGluRs将在其信号传导中使用更多的EF-hand Ca2+结合蛋白。在这里，我展示了钙结合蛋白1 （CaBP1）以Ca2+依赖的方式与CaM竞争性地结合到突触前III组mGluRs上，并且这种结合被蛋白激酶C （PKC）介导的这些受体的磷酸化所阻断。正如之前在CaM中显示的那样，这些结果表明CaBP1在突触前III组mGluRs信号串音中的重要性，其中包括许多分子，如cAMP， Ca2+， PKC， G蛋白和Munc18-1。然而，由于EF-hand钙结合蛋白的功能多样性是非凡的，如Ca2+通道的调节，CaBP1将提供一种独特的方式，通过该方式，突触前III组mGluRs微调突触传递。
Presynaptic group III metabotropic glutamate receptors (mGluRs) and Ca2+channels are the main neuronal activity-dependent regulators of synaptic vesicle release, and they use common molecules in their signaling cascades. Among these, calmodulin (CaM) and the related EF-hand Ca2+-binding proteins are of particular importance as sensors of presynaptic Ca2+, and a multiple of them are indeed utilized in the signaling of Ca2+channels. However, despite its conserved structure, CaM is the only known EF-hand Ca2+-binding protein for signaling by presynaptic group III mGluRs. Because the mGluRs and Ca2+channels reciprocally regulate each other and functionally converge on the regulation of synaptic vesicle release, the mGluRs would be expected to utilize more EF-hand Ca2+-binding proteins in their signaling. Here I show that calcium-binding protein 1 (CaBP1) bound to presynaptic group III mGluRs competitively with CaM in a Ca2+-dependent manner and that this binding was blocked by protein kinase C (PKC)-mediated phosphorylation of these receptors. As previously shown for CaM, these results indicate the importance of CaBP1 in signal cross talk at presynaptic group III mGluRs, which includes many molecules such as cAMP, Ca2+, PKC, G protein, and Munc18-1. However, because the functional diversity of EF-hand calcium-binding proteins is extraordinary, as exemplified by the regulation of Ca2+channels, CaBP1 would provide a distinct way by which presynaptic group III mGluRs fine-tune synaptic transmission.