Rivera Rocío, Rozas José Luis, Lerma Juan
Cellular and Systems Neurobiology, Instituto de Neurociencias de Alicante, CSIC-UMH, San Juan de Alicante, Spain.
EMBO J. 2007 Oct 17;26(20):4359-67. doi: 10.1038/sj.emboj.7601865. Epub 2007 Sep 27.
Agonists of kainate receptors (KARs) cause both the opening of the associated ion channels and the activation of signalling pathways driven by G-proteins and PKC. Here we report the existence of an unknown mechanism of KAR autoregulation, involving the interplay of this two signalling mechanisms. Repetitive activation of native KARs evoked the rundown of the ionotropic responses in a manner that was dependent on the activation of PKC. Experiments on recombinant GluR5 expressed in neuroblastoma cells indicated that KARs trigger the activation of PKC and induce the internalization of membrane receptors. This phenomenon depends on the PKC-mediated phosphorylation of serines 879 and 885 of the GluR5-2b subunits, since mutation of these two residues abolished internalization. These results reveal that the non-canonical signalling of KARs is associated with a sensitive mechanism that detects afferent activity. Such a mechanism represents an active way to limit overactivation of the KAR system, by regulating the number of KARs in the cell membrane.
红藻氨酸受体（KARs）激动剂可引起相关离子通道的开放以及由G蛋白和蛋白激酶C（PKC）驱动的信号通路的激活。在此，我们报告了一种未知的KAR自身调节机制的存在，该机制涉及这两种信号机制的相互作用。天然KARs的重复激活以依赖PKC激活的方式引起离子otropic反应的衰减。对在神经母细胞瘤细胞中表达的重组GluR5进行的实验表明，KARs触发PKC的激活并诱导膜受体的内化。这种现象取决于PKC介导的GluR5-2b亚基丝氨酸879和885的磷酸化，因为这两个残基的突变消除了内化。这些结果表明，KARs的非经典信号传导与一种检测传入活动的敏感机制相关。这种机制代表了一种通过调节细胞膜中KARs的数量来限制KAR系统过度激活的有效方式。
