Calcium-Sensing Receptor and Regulation of WNK Kinases in the Kidney
| Autor: | Yuri B. Porozov, Tatiana I Melnikova, Daria S Ostroverkhova, Vadim V. Tarasov, Kerim Mutig, Junda Hu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
calcium-sensing receptor 030232 urology & nephrology Parathyroid hormone chemistry.chemical_element Review Protein Serine-Threonine Kinases Calcium Kidney NKCC2 03 medical and health sciences 0302 clinical medicine with-no-lysine kinases medicine Animals Humans lcsh:QH301-705.5 Calcium metabolism NCC urogenital system Kinase Reabsorption distal nephron Nephrons General Medicine Cell biology 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) chemistry Calcium-sensing receptor Cotransporter Receptors Calcium-Sensing Signal Transduction |
| Zdroj: | Cells, Vol 9, Iss 1644, p 1644 (2020) Cells |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells9071644 |
| Popis: | The kidney is essential for systemic calcium homeostasis. Urinary calcium excretion can be viewed as an integrative renal response to endocrine and local stimuli. The extracellular calcium-sensing receptor (CaSR) elicits a number of adaptive reactions to increased plasma Ca2+ levels including the control of parathyroid hormone release and regulation of the renal calcium handling. Calcium reabsorption in the distal nephron of the kidney is functionally coupled to sodium transport. Apart from Ca2+ transport systems, CaSR signaling affects relevant distal Na+-(K+)-2Cl− cotransporters, NKCC2 and NCC. NKCC2 and NCC are activated by a kinase cascade comprising with-no-lysine [K] kinases (WNKs) and two homologous Ste20-related kinases, SPAK and OSR1. Gain-of-function mutations within the WNK-SPAK/OSR1-NKCC2/NCC pathway lead to renal salt retention and hypertension, whereas loss-of-function mutations have been associated with salt-losing tubulopathies such as Bartter or Gitelman syndromes. A Bartter-like syndrome has been also described in patients carrying gain-of-function mutations in the CaSR gene. Recent work suggested that CaSR signals via the WNK-SPAK/OSR1 cascade to modulate salt reabsorption along the distal nephron. The review presented here summarizes the latest progress in understanding of functional interactions between CaSR and WNKs and their potential impact on the renal salt handling and blood pressure. |
| Databáze: | OpenAIRE |
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