Chen Ying, McQuade Kyle J, Guan Xiao-Juan, Thomason Peter A, Wert Michael S, Stock Jeffry B, Cox Edward C
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Mol Biol Cell. 2007 Oct;18(10):4106-18. doi: 10.1091/mbc.e06-11-1006. Epub 2007 Aug 15.
Members of the Ras superfamily of small GTPases and the heterotrimeric G protein gamma subunit are methylated on their carboxy-terminal cysteine residues by isoprenylcysteine methyltransferase. In Dictyostelium discoideum, small GTPase methylation occurs seconds after stimulation of starving cells by cAMP and returns quickly to basal levels, suggesting an important role in cAMP-dependent signaling. Deleting the isoprenylcysteine methyltransferase-encoding gene causes dramatic defects. Starving mutant cells do not propagate cAMP waves in a sustained manner, and they do not aggregate. Motility is rescued when cells are pulsed with exogenous cAMP, or coplated with wild-type cells, but the rescued cells exhibit altered polarity. cAMP-pulsed methyltransferase-deficient cells that have aggregated fail to differentiate, but mutant cells plated in a wild-type background are able to do so. Localization of and signaling by RasG is altered in the mutant. Localization of the heterotrimeric Ggamma protein subunit was normal, but signaling was altered in mutant cells. These data indicate that isoprenylcysteine methylation is required for intercellular signaling and development in Dictyostelium.
小GTP酶的Ras超家族成员和异源三聚体G蛋白γ亚基在其羧基末端的半胱氨酸残基上被异戊二烯基半胱氨酸甲基转移酶甲基化。在盘基网柄菌中，小GTP酶甲基化在饥饿细胞被cAMP刺激后数秒内发生，并迅速恢复到基础水平，这表明其在cAMP依赖性信号传导中起重要作用。删除编码异戊二烯基半胱氨酸甲基转移酶的基因会导致严重缺陷。饥饿的突变细胞不能持续传播cAMP波，也不会聚集。当用外源性cAMP对细胞进行脉冲处理，或与野生型细胞共培养时，运动性得以恢复，但获救的细胞表现出极性改变。已聚集的经cAMP脉冲处理的甲基转移酶缺陷细胞无法分化，但接种在野生型背景中的突变细胞能够分化。突变体中RasG的定位和信号传导发生改变。异源三聚体Gγ蛋白亚基的定位正常，但突变细胞中的信号传导发生改变。这些数据表明，异戊二烯基半胱氨酸甲基化是盘基网柄菌细胞间信号传导和发育所必需的。
