Edmonds B T, Murray J, Condeelis J
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
J Biol Chem. 1995 Jun 23;270(25):15222-30. doi: 10.1074/jbc.270.25.15222.
ABP50, an F-actin bundling protein from Dictyostelium, is also the protein synthesis co-factor, elongation factor 1 alpha (EF1 alpha). Concomitant with cAMP stimulation in Dictyostelium is a cytoplasmic alkalinization (Aerts, R. J., DeWit, R. J. W., and Van Lookeren Campagne, M. M. (1987) FEBS Lett. 220, 366-370) and a redistribution of EF1 alpha (Dharmawardhane, S., Demma, M., Yang, F., and Condeelis, J. (1991) Cell Motil. Cytoskel. 20, 279-288). In addition, others have shown a correlation between intracellular pH and the level of protein synthesis in Dictyostelium (Aerts, R. J., Durston, A. J., and Moolenaar, W. H. (1985) Cell 43, 653-657). The present study investigates the relationship between pH and the F-actin binding properties of EF1 alpha. We found that increasing pH over the physiological range 6.2-7.8 causes a loss of EF1 alpha-mediated F-actin bundling and single filament binding, with corresponding increases in the amount of free EF1 alpha in vitro. Similar results also were obtained by cell fractionation and confocal immunofluorescence microscopy. The EF1 alpha binding constant (Kd) for F-actin is increased from 0.2 microM to > 2.2 microM over the same pH range. In addition, EF1 alpha-induced actin bundle formation is freely reversible by changes in pH. Thus, pH may be a potent modulator of cytoarchitecture in Dictyostelium and may also influence mRNA translation rates by modifying the interactions between the protein synthetic machinery and the actin cytoskeleton.
ABP50是一种来自盘基网柄菌的F-肌动蛋白成束蛋白,也是蛋白质合成辅因子延伸因子1α(EF1α)。在盘基网柄菌中,伴随cAMP刺激的是细胞质碱化(阿尔茨,R.J.,德维特,R.J.W.,和范·洛克莱伦·坎帕涅,M.M.(1987年)《欧洲生物化学学会联合会快报》220,366 - 370)以及EF1α的重新分布(达马瓦尔丹,S.,德马,M.,杨,F.,和康德利斯,J.(1991年)《细胞运动与细胞骨架》20,279 - 288)。此外,其他人已经表明盘基网柄菌细胞内pH与蛋白质合成水平之间存在相关性(阿尔茨,R.J.,达尔斯顿,A.J.,和穆勒纳尔,W.H.(1985年)《细胞》43,653 - 657)。本研究调查了pH与EF1α的F-肌动蛋白结合特性之间的关系。我们发现,在生理范围6.2 - 7.8内提高pH会导致EF1α介导的F-肌动蛋白成束和单丝结合丧失,同时体外游离EF1α的量相应增加。通过细胞分级分离和共聚焦免疫荧光显微镜也获得了类似结果。在相同pH范围内,EF1α与F-肌动蛋白的结合常数(Kd)从0.2微摩尔增加到>2.2微摩尔。此外,pH的变化可使EF1α诱导的肌动蛋白束形成自由逆转。因此pH可能是盘基网柄菌细胞结构的有力调节剂,也可能通过改变蛋白质合成机制与肌动蛋白细胞骨架之间的相互作用来影响mRNA翻译速率。