Parczyk K, Kondor-Koch C
Abteilung Molekulare Genetik der Universität, Frankfurt am Main/Bundesrepublik Deutschland.
Eur J Cell Biol. 1989 Apr;48(2):353-9.
The effect of pH on the secretion of the gp 80 glycoprotein complex and lysozyme from MDCK cells was examined by treatment of the cells with either NH4Cl, chloroquine or monensin. In untreated cells gp 80 is sorted with approximately 75% efficiency into the apical pathway. Lysozyme is secreted in a nonpolar fashion at both cell surfaces. Treatment of the cells with the drugs had nearly identical effects on the transport kinetics and on the ratio of the proteins released at the two plasma membrane domains. At increasing drug concentrations, the transport of both proteins to the apical and the basolateral cell surface was equally retarded. Furthermore, we observed a dose-dependent decrease in the amount of gp 80 and lysozyme released at the basolateral cell surface, which was accompanied by a nearly equivalent increase in the secretion of the two proteins at the apical plasma membrane domain. A twofold rise in the apical to basolateral ratio was already found at drug concentrations which only marginally affected the kinetics of transport. These results show that an increase in intravesicular pH not only redirects secretory proteins sorted into the basolateral pathway (Caplan et al. Nature, 329, 632 (1987] but also secretory proteins devoid of sorting information for that pathway, presumably by modulating the vesicular traffic to the basolateral cell surface.
通过用氯化铵、氯喹或莫能菌素处理细胞,研究了pH对MDCK细胞分泌gp 80糖蛋白复合物和溶菌酶的影响。在未处理的细胞中,gp 80以约75%的效率被分选到顶端途径。溶菌酶以非极性方式在细胞的两个表面分泌。用这些药物处理细胞对转运动力学以及在两个质膜结构域释放的蛋白质比例具有几乎相同的影响。随着药物浓度增加,两种蛋白质向顶端和基底外侧细胞表面的转运均同样受到抑制。此外,我们观察到基底外侧细胞表面释放的gp 80和溶菌酶量呈剂量依赖性减少,同时在顶端质膜结构域两种蛋白质的分泌几乎等量增加。在仅轻微影响转运动力学的药物浓度下,顶端与基底外侧的比例就已出现两倍的升高。这些结果表明,囊泡内pH的升高不仅会使分选到基底外侧途径的分泌蛋白重新定向(卡普兰等人,《自然》,第329卷,第632页[1987年]),而且还会使缺乏该途径分选信息的分泌蛋白重新定向,大概是通过调节向基底外侧细胞表面的囊泡运输来实现的。