Phospholipase C isozymes selectively couple to specific neurotransmitter receptors
Phospholipase C isozymes selectively couple to specific neurotransmitter receptors
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作者：
Kim, D;Jun, KS;Shin, HS
磷酸肌醇特异性磷脂酶 C-β (PLC-beta) 与鸟嘌呤核苷酸结合 G 蛋白偶联，可跨细胞膜转导多种细胞外信号。 PLC-β、β1-β4有四种同工酶，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-beta 1 和 PLC-beta 4 在大脑中的作用：我们发现 PLC beta 1(-/-) 小鼠出现癫痫，PLC beta 4(-/-) 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-β 1 主要通过与毒蕈碱乙酰胆碱受体偶联来参与大脑皮层和海马的信号转导，而 PLC-β 4 通过小脑中的代谢型谷氨酸受体发挥作用，这说明了如何使用 PLC-β 同工酶 在大脑中产生不同的功能。
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, beta 1-beta 4, but their functions in vivo are not known. Here we investigate the role of PLC-beta 1 and PLC-beta 4 in the brain by generating-null mutations in mice: we found that PLC beta 1(-/-) mice developed epilepsy and PLC beta 4(-/-) mice showed ataxia. We determined the molecular basis of these phenotypes and show that PLC-beta 1 is involved in signal transduction in the cerebral cortex and hippocampus by coupling pre-dominantly to the muscarinic acetylcholine receptor, whereas PLC-beta 4 works through the metabotropic glutamate receptor in the cerebellum, illustrating how PLC-beta isoenzymes are used to generate different functions in the brain.