Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia, USA.
Department of Cellular Biology, University of Georgia, Athens, Georgia, USA.
mSphere. 2019 Apr 3;4(2):e00045-19. doi: 10.1128/mSphere.00045-19.
Inorganic pyrophosphate (PP) is a by-product of biosynthetic reactions and has bioenergetic and regulatory roles in a variety of cells. Here we show that PP and other pyrophosphate-containing compounds, including polyphosphate (polyP), can stimulate sodium-dependent depolarization of the membrane potential and P conductance in oocytes expressing a or Na/P symporter. PP is not taken up by oocytes, and deletion of the TbPho91 SPX domain abolished its depolarizing effect. PP generated outward currents in Na/P-loaded giant vacuoles prepared from wild-type or Δ yeast strains expressing but not from the strains. Our results suggest that PP, at physiological concentrations, can function as a signaling molecule releasing P from vacuoles and acidocalcisomes. Acidocalcisomes, first described in trypanosomes and known to be present in a variety of cells, have similarities with vacuoles in their structure and composition. Both organelles share a Na/P symporter involved in P release to the cytosol, where it is needed for biosynthetic reactions. Here we show that PP, at physiological cytosolic concentrations, stimulates the symporter expressed in either oocytes or yeast vacuoles via its SPX domain, revealing a signaling role of this molecule.
无机焦磷酸（PP）是生物合成反应的副产物，在各种细胞中具有生物能量和调节作用。在这里，我们表明 PP 和其他含有焦磷酸的化合物，包括多磷酸盐（polyP），可以刺激表达 a 或 Na/P 协同转运蛋白的卵母细胞中的膜电位和 P 电导的钠依赖性去极化。PP 不会被卵母细胞摄取，并且缺失 TbPho91 SPX 结构域会使其去极化作用丧失。PP 在从野生型或 Δ酵母菌株制备的表达 但不是从 菌株表达的 Na/P 加载巨型液泡中产生外向电流。我们的结果表明，在生理浓度下，PP 可以作为一种信号分子，从 液泡和 酸钙体中释放 P。酸钙体，首先在原生动物中描述，并已知存在于各种细胞中，在结构和组成上与 液泡相似。这两个细胞器都有一个参与将 P 释放到细胞质中的 Na/P 协同转运蛋白，细胞质中需要 P 进行生物合成反应。在这里，我们表明，在生理细胞溶质浓度下，PP 通过其 SPX 结构域刺激在卵母细胞或酵母液泡中表达的协同转运蛋白，揭示了这种分子的信号作用。
