Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, DC, USA.
Department of Biomedical Engineering, Laboratory for Fluorescence Dynamics, University of California at Irvine, Irvine, CA, USA.
Pflugers Arch. 2019 Apr;471(4):533-542. doi: 10.1007/s00424-018-02249-w. Epub 2019 Jan 6.
The cloning of the renal NaPi-2a (SLC34A1) and NaPi-2c (SLC34A3) phosphate transporters has made it possible to characterize the molecular and biophysical regulation of renal proximal tubular reabsorption of inorganic phosphate (Pi). Dietary factors, such as Pi and K, and several hormones and phosphatonins, including parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and glucocorticoids, regulate the transporters through various transcriptional, translational, and post-translational mechanisms that involve acute trafficking via endocytosis or exocytosis, interactions with PDZ domain proteins, lipid microdomains, and diffusion and clustering in the apical brush border membrane. The visualization of these trafficking events by means of novel microscopy techniques that includes fluorescence lifetime imaging microscopy (FLIM), Förster resonance energy transfer (FRET), fluctuation correlation spectroscopy (FCS), and modulation tracking (MT), is the primary focus of this review.
肾 NaPi-2a(SLC34A1)和 NaPi-2c(SLC34A3)磷酸转运蛋白的克隆使得对肾脏近端小管对无机磷酸盐(Pi)的重吸收的分子和生物物理调节进行特征分析成为可能。饮食因素,如 Pi 和 K,以及几种激素和磷酸酯,包括甲状旁腺激素(PTH)、成纤维细胞生长因子 23(FGF23)和糖皮质激素,通过涉及内吞作用或胞吐作用的各种转录、翻译和翻译后机制来调节转运蛋白,与 PDZ 结构域蛋白、脂质微区以及在顶膜刷状缘中的扩散和聚集相互作用。通过包括荧光寿命成像显微镜(FLIM)、Förster 共振能量转移(FRET)、波动相关光谱(FCS)和调制跟踪(MT)在内的新型显微镜技术对这些运输事件进行可视化,是本综述的主要重点。