Visualizing the regulation of SLC34 proteins at the apical membrane

Pflugers Arch. 2019 Apr;471(4):533-542. doi: 10.1007/s00424-018-02249-w. Epub 2019 Jan 6.

Abstract

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.

Keywords: Fluctuation correlation spectroscopy (FCS); Fluorescence lifetime imaging microscopy (FLIM); Förster resonance energy transfer (FRET); NaPi transporter diffusion and clustering; NaPi-PDZ protein interactions; NaPi-lipid interactions.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Membrane / metabolism*
  • Fibroblast Growth Factor-23
  • Humans
  • Kidney Tubules, Proximal / metabolism
  • Phosphates / metabolism
  • Protein Transport / physiology
  • Sodium-Phosphate Cotransporter Proteins, Type II / metabolism*

Substances

  • FGF23 protein, human
  • Phosphates
  • Sodium-Phosphate Cotransporter Proteins, Type II
  • Fibroblast Growth Factor-23