Internalization of renal type IIc Na-Pi cotransporter in response to a high-phosphate diet.
Internalization of renal type IIc Na-Pi cotransporter in response to a high-phosphate diet.
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DOI：
10.1152/ajprenal.00097.2004
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发表时间：
2005-03
期刊：
影响因子：
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通讯作者：
H. Segawa;S. Yamanaka;Mikiko Ito;M. Kuwahata;M. Shono;Tadashi Yamamoto;K. Miyamoto
中科院分区：
文献类型：
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作者：
H. Segawa;S. Yamanaka;Mikiko Ito;M. Kuwahata;M. Shono;Tadashi Yamamoto;K. Miyamoto
膳食磷酸盐水平调节肾脏刷状缘IIa型Na-Pi协同转运蛋白。另一种钠-磷共转运蛋白，IIc型，与IIa型钠-磷共转运蛋白共定位于肾近端小管细胞的顶膜。本研究的目的是确定饮食中的磷酸盐水平是否也能快速调节IIc型钠-磷协同转运蛋白。与正常Pi饮食的大鼠相比，长期喂食低Pi饮食的大鼠的IIa型和IIc型转运蛋白水平增加。开始高磷饮食后两小时，IIa型转运蛋白水平下降，而IIc型蛋白水平保持不变。蛋白质印迹分析的刷状缘膜4小时后开始高磷饮食表明，IIc型转运蛋白水平显着降低，和免疫组化显示易位的IIc型免疫反应信号从整个刷状缘的根尖下膜。膜分离的研究表明，顶膜IIc型蛋白的减少，而总皮质IIc型蛋白的变化，这是兼容的IIc型蛋白从顶膜的致密膜部分的重新分配。微管破坏剂秋水仙碱防止这种减少顶端IIc型转运蛋白在顶端膜，但没有影响IIa型转运蛋白水平。这些数据表明，IIc型钠-磷协同转运蛋白水平迅速调节快速适应饮食中的磷在微管依赖性的方式。此外，IIc型转运蛋白的内化机制不同于IIa型转运蛋白。
Dietary phosphate levels regulate the renal brush-border type IIa Na-Pi cotransporter. Another Na-Pi cotransporter, type IIc, colocalizes with type IIa Na-Pi cotransporter in the apical membrane of renal proximal tubular cells. The goal of the present study was to determine whether dietary phosphate levels also rapidly regulate the type IIc Na-Pi cotransporter. Type IIa and type IIc transporter protein levels were increased in rats chronically fed a low-Pi diet compared with those fed a normal-Pi diet. Two hours after beginning a high-Pi diet, type IIa transporter levels were decreased, whereas type IIc protein levels remained unchanged. Western blot analysis of brush-border membrane prepared 4 h after beginning a high-Pi diet showed a significant reduction in type IIc transporter protein levels, and immunohistochemistry showed translocation of the type IIc-immunoreactive signal from the entire brush border to subapical membrane. Membrane fractionation studies revealed a decrease in apical membrane type IIc protein without changes in total cortical type IIc protein, which is compatible with redistribution of type IIc protein from the apical membrane to the dense membrane fraction. The microtubule-disrupting reagent colchicine prevented this reduction in apical type IIc transporter at the apical membrane but had no effect on type IIa transporter levels. These data suggest that the type IIc Na-Pi cotransporter level is rapidly regulated by rapid adaptation to dietary Pi in a microtubule-dependent manner. Furthermore, the mechanisms of the internalization of the type IIc transporter are distinct from those of the type IIa transporter.