Human Na+/H+ exchanger isoform 6 is found in recycling endosomes of cells, not in mitochondria
Human Na+/H+ exchanger isoform 6 is found in recycling endosomes of cells, not in mitochondria
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DOI：
10.1152/ajpcell.00420.2001
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发表时间：
2002-05-01
影响因子：
5.5
通讯作者：
Rao, R
中科院分区：
文献类型：
--
作者：
Brett, CL;Wei, Y;Rao, R
自从在酵母中发现第一个胞内Na+/H+交换器Nhx 1以来，已经在植物中克隆和表征了多个同源物。总之，在这些生物体中的研究表明，Nhx 1位于细胞的prevacuolar/vacuolar隔室，在那里它隔离Na+进入液泡，调节囊泡内pH值，并有助于液泡生物发生。相反，Nhx 1的人类同源物，Na+/H+交换器同种型6（NHE 6），已被报道定位于线粒体时，瞬时表达为与绿色荧光蛋白的融合。这一结果值得重新评估，因为它与系统发育分析的预测相冲突。在这里，我们证明，当表位标记的NHE 6在培养的哺乳动物细胞中瞬时表达，它不与线粒体标记物共定位。它也不与溶酶体、晚期内体、高尔基体网络或高尔基体池的标记物共定位。相反，NHE 6分布在再循环区室中，并短暂出现在质膜上。这些结果表明，像它的同系物在酵母和植物，NHE 6是一个内体Na+/H+交换器，可以调节囊泡内的pH值和体积，并有助于溶酶体的生物合成。
Since the discovery of the first intracellular Na+/H+ exchanger in yeast, Nhx1, multiple homologs have been cloned and characterized in plants. Together, studies in these organisms demonstrate that Nhx1 is located in the prevacuolar/vacuolar compartment of cells where it sequesters Na+ into the vacuole, regulates intravesicular pH, and contributes to vacuolar biogenesis. In contrast, the human homolog of Nhx1, Na+/H+ exchanger isoform 6 (NHE6), has been reported to localize to mitochondria when transiently expressed as a fusion with green fluorescent protein. This result warrants reevaluation because it conflicts with predictions from phylogenetic analyses. Here we demonstrate that when epitope-tagged NHE6 is transiently expressed in cultured mammalian cells, it does not colocalize with mitochondrial markers. It also does not colocalize with markers of the lysosome, late endosome, trans-Golgi network, or Golgi cisternae. Rather, NHE6 is distributed in recycling compartments and transiently appears on the plasma membrane. These results suggest that, like its homologs in yeast and plants, NHE6 is an endosomal Na+/H+ exchanger that may regulate intravesicular pH and volume and contribute to lysosomal biogenesis.