Alemany S, García Gil M, Mato J M
Proc Natl Acad Sci U S A. 1980 Dec;77(12):6996-9. doi: 10.1073/pnas.77.12.6996.
In Dictyostelium discoideum, the chemoattractant cyclic AMP activates the enzyme guanylate cyclase, giving a brief up to 10-fold increase in the intracellular cyclic GMP content. The addition of physiological cyclic GMP concentrations to a homogenate of D. discoideum cells markedly increased the incorporation of the 3H-labeled methyl group from S-adenosyl-L-[methyl-3H]methionine into mono- and dimethylated phosphatidylethanolamine and phosphatidylcholine. Lipid methylation was inhibited by S-adenosyl-L-homocysteine, which inhibits transmethylation. When whole cells prelabeled with L-[methyl-3H]methionine were exposed to cyclic AMP, a rapid transient increase in the amount of [methyl-3H]phosphatidylcholine was observed. The time course of [methyl-3H]phosphatidylcholine formation agrees with its being mediated by the intracellular increase in cyclic GMP originating during chemotactic stimulation. Addition of the 8-Br derivative of cyclic GMP to whole cells also increased the levels of labeled phosphatidylcholine. It is therefore likely that cyclic GMP contributes to chemotaxis by regulating membrane function via phospholipid methylation.
在盘基网柄菌中,趋化因子环磷酸腺苷(cAMP)激活鸟苷酸环化酶,使细胞内的环磷酸鸟苷(cGMP)含量短暂增加多达10倍。向盘基网柄菌细胞匀浆中添加生理浓度的cGMP,显著增加了3H标记的甲基从S-腺苷-L-[甲基-3H]甲硫氨酸掺入单甲基化和二甲基化磷脂酰乙醇胺及磷脂酰胆碱的量。脂质甲基化受到S-腺苷-L-高半胱氨酸的抑制,而S-腺苷-L-高半胱氨酸会抑制转甲基作用。当用L-[甲基-3H]甲硫氨酸预标记的完整细胞暴露于cAMP时,观察到[甲基-3H]磷脂酰胆碱的量迅速短暂增加。[甲基-3H]磷脂酰胆碱形成的时间进程与其由趋化刺激过程中产生的细胞内cGMP增加所介导一致。向完整细胞中添加cGMP的8-溴衍生物也增加了标记的磷脂酰胆碱水平。因此,cGMP很可能通过磷脂甲基化调节膜功能来促进趋化作用。