Kim D, Jun K S, Lee S B, Kang N G, Min D S, Kim Y H, Ryu S H, Suh P G, Shin H S
Department of Life Science, Pohang University of Science and Technology, Republic of Korea.
Nature. 1997 Sep 18;389(6648):290-3. doi: 10.1038/38508.
A variety of extracellular signals are transduced across the cell membrane by the enzyme phosphoinositide-specific phospholipase C-beta (PLC-beta) coupled with guanine-nucleotide-binding G proteins. There are four isoenzymes of PLC-beta, beta1-beta4, but their functions in vivo are not known. Here we investigate the role of PLC-beta1 and PLC-beta4 in the brain by generating null mutations in mice: we found that PLCbeta1-/- mice developed epilepsy and PLCbeta4-/- mice showed ataxia. We determined the molecular basis of these phenotypes and show that PLC-beta1 is involved in signal transduction in the cerebral cortex and hippocampus by coupling predominantly to the muscarinic acetylcholine receptor, whereas PLC-beta4 works through the metabotropic glutamate receptor in the cerebellum, illustrating how PLC-beta isoenzymes are used to generate different functions in the brain.
多种细胞外信号通过与鸟嘌呤核苷酸结合G蛋白偶联的磷酸肌醇特异性磷脂酶C-β（PLC-β）跨细胞膜进行转导。PLC-β有四种同工酶，即β1-β4，但它们在体内的功能尚不清楚。在这里，我们通过在小鼠中产生无效突变来研究PLC-β1和PLC-β4在大脑中的作用：我们发现PLCβ1-/-小鼠会发生癫痫，而PLCβ4-/-小鼠表现出共济失调。我们确定了这些表型的分子基础，并表明PLC-β1主要通过与毒蕈碱型乙酰胆碱受体偶联参与大脑皮层和海马体的信号转导，而PLC-β4则通过小脑的代谢型谷氨酸受体发挥作用，这说明了PLC-β同工酶是如何在大脑中产生不同功能的。
