REGULATION OF ENDOCYTIC PH BY THE NA+,K+-ATPASE IN LIVING CELLS
REGULATION OF ENDOCYTIC PH BY THE NA+,K+-ATPASE IN LIVING CELLS
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DOI：
10.1073/pnas.86.2.544
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发表时间：
1989-01-01
影响因子：
11.1
通讯作者：
MURPHY, RF
中科院分区：
文献类型：
--
作者：
CAIN, CC;SIPE, DM;MURPHY, RF
内吞的配体的酸化是双相的，快速下降到pH 6，然后缓慢下降到pH 5。转铁蛋白酸化的连续测量已经证实，早期（预分选）内体中的pH最小值约为pH 6。基于体外内体酸化的测量，已经提出，早期内体中的pH受到Na+，K+-ATP酶的内化的限制，其在该隔室中产生正的膜电位[Fuchs，R.，Schmid，S.和Mellman，I.等人（1989）Proc. Acad. Sci. USA 86，539-543]。我们提出了两条证据，强烈暗示Na+，K+-ATP酶作为一个主要的调节元件的内吞pH在体内。首先，哇巴因，Na+，K+-ATP酶的特异性抑制剂，干扰早期内吞隔室的酸化调节。转铁蛋白通常迅速酸化至pH 6.0-6.2，然后在回收过程中碱化。在哇巴因的存在下，含转铁蛋白的内体的最低pH从6.0-6.2降低到6.0-6.2。
Acidification of endocytosed ligands destined for lysosomes is biphasic, with a rapid drop to pH 6, followed by a slow decrease to pH 5. Continuous measurements of transferrin acidication have confirmed that the pH minimum in early (presorting) endosomes is approximately pH 6. On the basis of measurements of endosomal acidification in vitro, it has been proposed that the pH in the early endosome is limited by the internalization of the Na+,K+-ATPase, which generates an interior-positive membrane potential in this compartment [Fuchs, R., Schmid, S. and Mellman, I. (1989) Proc. Natl. Acad. Sci. USA 86, 539-543]. We present two lines of evidence that strongly implicate the Na+,K+-ATPase as a major regulatory element of endocytic pH in vivo. First, ouabain, a specific inhibitor of the Na+,K+-ATPase, interferes with the regulation of acidification in early endocytic compartments. Transferrin is normally rapidly acidified to pH 6.0-6.2, followed by alkalinization during recycling. In the presence of ouabain, the minimum pH of transferrin-containing endosomes decreases from 6.0-6.2 to