Yun C W, Tamaki H, Nakayama R, Yamamoto K, Kumagai H
Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.
Biochem Biophys Res Commun. 1998 Nov 9;252(1):29-33. doi: 10.1006/bbrc.1998.9600.
How cells monitor the availability of nutrition and transduce signals is a fundamental, unanswered question. We have found that Gpr1p, a recently identified G-protein (Gpa2p) coupled receptor in yeast Saccharomyces cerevisiae, regulate the cellular cAMP level in response to glucose. The glucose-induced higher cAMP level found in the strain with GPA2 in multicopy plasmid decreased by deletion of GPR1 gene. A transient increase of cAMP in response to glucose was not observed in a Deltagpr1 mutant strain and this defect was complemented and restored by introducing GPR1 gene with YCp vector. Gpr1p was also required for the increase of cAMP in response to other fermentable sugars. Both membrane proximal regions o the third cytosolic loop in Gpr1p, which has been shown to be important for coupling to G-proteins, were also required for glucose-induced transient increase of cAMP. Our findings suggest that Gpr1p is part of the nutrition sensing machinery most likely acting as a receptor to monitor glucose as well as other fermentable sugars and regulate cellular cAMP levels.
细胞如何监测营养物质的可用性并传导信号是一个基本的、尚未解决的问题。我们发现,Gpr1p是酿酒酵母中最近鉴定出的一种与G蛋白(Gpa2p)偶联的受体,它可响应葡萄糖调节细胞内cAMP水平。在多拷贝质粒中带有GPA2的菌株中发现的葡萄糖诱导的较高cAMP水平,在缺失GPR1基因后降低。在Deltagpr1突变菌株中未观察到响应葡萄糖的cAMP瞬时增加,通过用YCp载体导入GPR1基因可弥补并恢复此缺陷。Gpr1p对于响应其他可发酵糖而增加cAMP也是必需的。Gpr1p中第三胞质环的两个膜近端区域,已证明它们对于与G蛋白偶联很重要,对于葡萄糖诱导的cAMP瞬时增加也是必需的。我们的研究结果表明,Gpr1p是营养感知机制的一部分,很可能作为一种受体来监测葡萄糖以及其他可发酵糖,并调节细胞内cAMP水平。