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Distinct and overlapping RGS14 and RGS12 actions regulate NPT2A-mediated phosphate transport.

W Bruce Sneddon1, Suneela Ramineni2, G Emme Van Doorn2

  • 1Laboratory for GPCR Biology, Departments of Pharmacology and Chemical Biology, USA.

Biochemical and Biophysical Research Communications
|September 18, 2024
PubMed
Summary
This summary is machine-generated.

Regulator of G protein signaling-12 (RGS12) binds to NHERF1 and NPT2A, regulating phosphate transport. RGS12, like RGS14, inhibits hormone-sensitive phosphate uptake in kidney cells.

Keywords:
Hormone regulationPhosphate transportRGS12RGS14

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Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • Parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) regulate serum phosphate levels by controlling the renal Na-phosphate transporter NPT2A.
  • This regulation involves the PDZ scaffold protein NHERF1 and the regulator of G protein signaling-14 (RGS14).
  • RGS14 contains a PDZ ligand that binds NHERF1, influencing phosphate transport.

Purpose of the Study:

  • To characterize the interaction of RGS12 with NHERF1 and NPT2A.
  • To investigate the functional role of RGS12 in hormone-regulated phosphate transport.
  • To compare the activity of RGS12 with RGS14 in controlling phosphate homeostasis.

Main Methods:

  • Immunoblotting to detect RGS12 binding to NHERF1.
  • Structural analysis to determine NPT2A interaction with RGS12 fragments.
  • Opossum kidney proximal tubule cell cultures for phosphate uptake assays.
  • Transfection studies with RGS14 and RGS12 to assess their effects on hormone-sensitive phosphate transport.

Main Results:

  • RGS12's C-terminal PDZ ligand binds to NHERF1.
  • Full-length RGS12 and its upstream fragment bind NPT2A, while RGS14 does not interact with NPT2A.
  • PTH and FGF23 inhibited phosphate uptake, an effect abolished by RGS14 or RGS12 transfection.
  • RGS12's inhibitory activity on phosphate transport is located in its downstream region and is comparable to RGS14.
  • A kidney-expressed RGS12 splice variant (RGS12(667-1447)) may play a role in phosphate transport regulation.

Conclusions:

  • RGS12 interacts with both NHERF1 and NPT2A, suggesting a role in phosphate transport regulation.
  • RGS12 functions similarly to RGS14 in inhibiting PTH- and FGF23-mediated phosphate uptake.
  • The RGS12(667-1447) splice variant is a key player in the kidney's regulation of phosphate homeostasis.