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Visualizing the regulation of SLC34 proteins at the apical membrane

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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.

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Acknowledgements

The authors also acknowledge the valuable contributions of several investigators in the Enrico Gratton, Moshe Levi, and Heini Murer labs that made these studies possible.

Funding

The studies in this review were supported by the National Institute of General Medical Sciences (NIGMS) NIH grant 2P41GM103540 to Enrico Gratton and NIDDK National Institutes of Health grant R01 DK066029 to Moshe Levi.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, DC, USA

    Moshe Levi

  2. Department of Biomedical Engineering, Laboratory for Fluorescence Dynamics, University of California at Irvine, Irvine, CA, USA

    Enrico Gratton

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  1. Moshe Levi
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  2. Enrico Gratton
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Correspondence to Moshe Levi.

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Levi, M., Gratton, E. Visualizing the regulation of SLC34 proteins at the apical membrane. Pflugers Arch - Eur J Physiol 471, 533–542 (2019). https://doi.org/10.1007/s00424-018-02249-w

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