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Identifying the localization and exploring a functional role for Gprc5c in the kidney
Premraj Rajkumar1, Boyoung Cha2, Jianyi Yin2
1Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Summary
The Gprc5c receptor is found in kidney tubules and helps regulate acid-base balance by controlling the activity of Na+/H+ exchanger 3 (NHE3), impacting systemic pH homeostasis.
Area of Science:
- Nephrology
- Physiology
- Molecular Biology
Background:
- Orphan G protein-coupled receptors (GPCRs) offer potential for novel physiological discoveries.
- Gprc5c is highly expressed in the kidney, suggesting a role in renal function.
- Understanding Gprc5c's function is crucial for insights into kidney physiology.
Purpose of the Study:
- To determine the renal localization of Gprc5c.
- To investigate the physiological role of Gprc5c using knockout mice.
- To elucidate Gprc5c's mechanism in regulating acid-base homeostasis.
Main Methods:
- Immunohistochemistry for Gprc5c localization in mouse, rat, and human kidneys.
- Physiological assessment of Gprc5c knockout (KO) and wild-type (WT) mice, including blood and urine pH.
- In vitro assays (GPCR internalization, BCECF assay) and in vivo imaging (2-photon microscopy) to assess Gprc5c and Na+/H+ exchanger 3 (NHE3) activity.
Main Results:
- Gprc5c localizes to the apical membrane of renal proximal tubules (PTs) across species.
- Gprc5c KO mice exhibit altered acid-base balance: lower blood pH, higher urine pH, and reduced urinary titratable acids.
- Gprc5c activation by alkaline pH increases NHE3 activity, which is impaired in Gprc5c KO mice.
Conclusions:
- Gprc5c plays a significant role in renal acid-base homeostasis.
- Gprc5c modulates systemic pH by regulating NHE3 activity in renal PTs.
- Gprc5c is a key mediator in the kidney's contribution to maintaining overall body pH balance.
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