Tu J C, Xiao B, Yuan J P, Lanahan A A, Leoffert K, Li M, Linden D J, Worley P F
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Neuron. 1998 Oct;21(4):717-26. doi: 10.1016/s0896-6273(00)80589-9.
Group I metabotropic glutamate receptors (mGluRs) activate PI turnover and thereby trigger intracellular calcium release. Previously, we demonstrated that mGluRs form natural complexes with members of a family of Homer-related synaptic proteins. Here, we present evidence that Homer proteins form a physical tether linking mGluRs with the inositol trisphosphate receptors (IP3R). A novel proline-rich "Homer ligand" (PPXXFr) is identified in group 1 mGluRs and IP3R, and these receptors coimmunoprecipitate as a complex with Homer from brain. Expression of the IEG form of Homer, which lacks the ability to cross-link, modulates mGluR-induced intracellular calcium release. These studies identify a novel mechanism in calcium signaling and provide evidence that an IEG, whose expression is driven by synaptic activity, can directly modify a specific synaptic function.
I 型代谢型谷氨酸受体（mGluRs）激活磷脂酰肌醇代谢并由此触发细胞内钙释放。此前，我们证明 mGluRs 与 Homer 相关突触蛋白家族成员形成天然复合物。在此，我们提供证据表明 Homer 蛋白形成了一个将 mGluRs 与肌醇三磷酸受体（IP3R）连接起来的物理连接物。在 I 型 mGluRs 和 IP3R 中鉴定出一种新型富含脯氨酸的“Homer 配体”（PPXXFr），并且这些受体与 Homer 作为一种复合物从大脑中共免疫沉淀。缺乏交联能力的 Homer 的 IEG 形式的表达调节 mGluR 诱导的细胞内钙释放。这些研究确定了钙信号传导中的一种新机制，并提供证据表明一种由突触活动驱动其表达的 IEG 可以直接改变特定的突触功能。
