Heterodimerization of calcium sensing receptors with metabotropic glutamate receptors in neurons
Heterodimerization of calcium sensing receptors with metabotropic glutamate receptors in neurons
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DOI：
10.1074/jbc.m105662200
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发表时间：
2001-10-19
影响因子：
4.8
通讯作者：
Breitwieser, GE
中科院分区：
文献类型：
--
作者：
Gama, L;Wilt, SG;Breitwieser, GE
钙敏感(CAR)和第一类代谢性谷氨酸受体在脑内呈现重叠的表达模式，并共享共同的信号转导途径。为了确定CAR和I组代谢性谷氨酸受体(MGluR)(mGluR1a和mGluR5)是否能形成异二聚体，我们从牛脑中免疫沉淀CAR并观察mGluR1a的共沉淀。CAR和mGluR1α共同定位于海马神经元和小脑神经元，但在其他脑区单独表达。在HEK-293细胞中的体外转染研究证实了CAR：mGluR1α(CAR：mGluR5)相互作用的特异性和二硫键连接的性质。与CAR：CAR同源二聚体相比，CAR：mGluR1α(CAR：mGluR5)异二聚体通过Hmer 1c的转运发生了变化。当CAR：mGluR1α异源二聚体存在时，CAR对谷氨酸介导的内化变得敏感。这些结果证明了CAR与I组mGluRs的跨家族共价异二聚化，并增加了CAR在神经功能调节中的潜在作用(S)。
Calcium sensing (CaR) and Group I metabotropic glutamate receptors exhibit overlapping expression patterns in brain, and share common signal transduction pathways. To determine whether CaR and Group I metabotropic glutamate receptors (mGluRs) (mGluR1 alpha and mGluR5) can form heterodimers, we immunoprecipitated CaR from bovine brain and observed co-precipitation of mGluR1a. CaR and mGluR1 alpha co-localize in hippocampal and cerebellar neurons, but are expressed separately in other brain regions. In vitro transfection studies in HEK-293 cells established the specificity and disulfide-linked nature of the CaR:mGluR1 alpha (CaR: mGluR5) interactions. CaR:mGluR1 alpha (CaR:mGluR5) heterodimers exhibit altered trafficking via Homer 1c when compared with CaR:CaR homodimers. CaR becomes sensitive to glutamate-mediated internalization when present in CaR:mGluR1 alpha heterodimers. These results demonstrate cross-family covalent heterodimerization of CaR with Group I mGluRs, and increase the potential role(s) for CaR in modulating neuronal function.