Geering K, Theulaz I, Verrey F, Häuptle M T, Rossier B C
Institut de Pharmacologie de l'Université de Lausanne, Switzerland.
Am J Physiol. 1989 Nov;257(5 Pt 1):C851-8. doi: 10.1152/ajpcell.1989.257.5.C851.
In all cellular systems studied so far, the catalytic alpha- and the glycosylated beta-subunit of Na+-K+-ATPase are coordinately synthesized and are assembled into stoichiometric alpha, beta-complexes. In contrast to these data, in this study we show that the fully grown oocyte of Xenopus laevis synthesizes much less beta-subunit than alpha-subunit. The alpha-subunit produced in excess over the beta-subunit is membrane associated but highly trypsin sensitive and can be compared with the immature alpha-subunit population identified in epithelial cells immediately after synthesis (K. Geering, J. P. Kraehenbuhl, and B.C. Rossier, J. Cell Biol. 105: 2613-2619, 1987). The Xenopus oocyte thus turns out to be a unique system to study the functional role of the beta-subunit. Injection of beta-subunit-specific mRNA transcribed in vitro from a beta-cDNA clone (derived from Xenopus kidney, A6 cells) into oocytes results in translation of a glycosylated beta-subunit. The synthesis of this exogenous beta-subunit increases significantly the proportion of trypsin-resistant oocyte alpha-subunits able to perform cation-dependent conformational changes. In addition, 25-65% more ouabian binding sites are expressed at the plasma membrane in beta-mRNA-injected oocytes. In contrast, newly synthesized alpha-subunit translated after injection of size-fractionated mRNA enriched in alpha-mRNA remains trypsin sensitive as the oocyte alpha-subunit. These data suggest that association of the beta-subunit to the alpha-subunit provokes a structural rearrangement of the alpha-subunit that might be a first step toward the functional maturation of the Na+-K+-ATPase and its expression at the plasma membrane.
在迄今为止研究的所有细胞系统中,钠钾ATP酶的催化α亚基和糖基化β亚基是协同合成的,并组装成化学计量的α、β复合物。与这些数据相反,在本研究中我们发现,非洲爪蟾完全成熟的卵母细胞合成的β亚基比α亚基少得多。过量产生的α亚基与膜相关,但对胰蛋白酶高度敏感,可与合成后立即在上皮细胞中鉴定出的未成熟α亚基群体相比较(K. 吉林、J. P. 克雷亨布尔和B. C. 罗西耶,《细胞生物学杂志》105: 2613 - 2619, 1987)。因此,非洲爪蟾卵母细胞成为研究β亚基功能作用的独特系统。将从β - cDNA克隆(源自非洲爪蟾肾脏A6细胞)体外转录的β亚基特异性mRNA注射到卵母细胞中,会导致糖基化β亚基的翻译。这种外源性β亚基的合成显著增加了能够进行阳离子依赖性构象变化的抗胰蛋白酶卵母细胞α亚基的比例。此外,注射β - mRNA的卵母细胞在质膜上表达的哇巴因结合位点多25% - 65%。相比之下,注射富含α - mRNA的大小分级mRNA后新合成的α亚基,与卵母细胞α亚基一样对胰蛋白酶敏感。这些数据表明,β亚基与α亚基的结合引发了α亚基的结构重排,这可能是钠钾ATP酶功能成熟及其在质膜上表达的第一步。