Evidence for a regulated Ca2+ entry in proximal tubular cells and its implication in calcium stone formation

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Abstract: Calcium phosphate (CaP) crystals, which begin to form in the early segments of the loop of Henle (LOH), are known to act as precursors for calcium stone formation. The proximal tubule (PT), which is just upstream of the LOH and is a major site for Ca2+ reabsorption, could be a regulator o...

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Autores principales: Ibeh, Cliff Lawrence, Yiu, Allen J., Kanaras, Yianni L., Paal, Edina, Birnbaumer, Lutz, Jose, Pedro A., Bandyopadhyay, Bidhan C.
Formato: Artículo
Lenguaje:Inglés
Publicado: The Company of Biologists 2020
Materias:
NEFROLOGIA
UROLITIASIS
CALCIO
RIÑON
MEDICINA
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/9396
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139-123456789-9396
record_format dspace
spelling I33-R139-123456789-93962024-03-26T10:52:10Z Evidence for a regulated Ca2+ entry in proximal tubular cells and its implication in calcium stone formation Ibeh, Cliff Lawrence Yiu, Allen J. Kanaras, Yianni L. Paal, Edina Birnbaumer, Lutz Jose, Pedro A. Bandyopadhyay, Bidhan C. NEFROLOGIA UROLITIASIS CALCIO RIÑON MEDICINA Abstract: Calcium phosphate (CaP) crystals, which begin to form in the early segments of the loop of Henle (LOH), are known to act as precursors for calcium stone formation. The proximal tubule (PT), which is just upstream of the LOH and is a major site for Ca2+ reabsorption, could be a regulator of such CaP crystal formation. However, PT Ca2+ reabsorption is mostly described as being paracellular. Here, we show the existence of a regulated transcellular Ca2+ entry pathway in luminal membrane PT cells induced by Ca2+-sensing receptor (CSR, also known as CASR)-mediated activation of transient receptor potential canonical 3 (TRPC3) channels. In support of this idea, we found that both CSR and TRPC3 are physically and functionally coupled at the luminal membrane of PT cells. More importantly, TRPC3-deficient mice presented with a deficiency in PT Ca2+ entry/transport, elevated urinary [Ca2+], microcalcifications in LOH and urine microcrystals formations. Taken together, these data suggest that a signaling complex comprising CSR and TRPC3 exists in the PT and can mediate transcellular Ca2+ transport, which could be critical in maintaining the PT luminal [Ca2+] to mitigate formation of the CaP crystals in LOH and subsequent formation of calcium stones. 2020-02-14T00:38:19Z 2020-02-14T00:38:19Z 2019 Artículo Ibeh, C., Yiu, A., Kanaras, Y., et al. Evidence for a regulated Ca2+ entry in proximal tubular cells and its implication in calcium stone formation [en línea]. Journal of Cell Science. 2019, 132. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/9396 1477-9137 (en línea) 0021-9533 (impreso) https://repositorio.uca.edu.ar/handle/123456789/9396 10.1242/jcs.225268 30910829 eng Acceso Abierto http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf The Company of Biologists Journal of Cell Science. 2019, 132
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic NEFROLOGIA
UROLITIASIS
CALCIO
RIÑON
MEDICINA
spellingShingle NEFROLOGIA
UROLITIASIS
CALCIO
RIÑON
MEDICINA
Ibeh, Cliff Lawrence
Yiu, Allen J.
Kanaras, Yianni L.
Paal, Edina
Birnbaumer, Lutz
Jose, Pedro A.
Bandyopadhyay, Bidhan C.
Evidence for a regulated Ca2+ entry in proximal tubular cells and its implication in calcium stone formation
topic_facet NEFROLOGIA
UROLITIASIS
CALCIO
RIÑON
MEDICINA
description Abstract: Calcium phosphate (CaP) crystals, which begin to form in the early segments of the loop of Henle (LOH), are known to act as precursors for calcium stone formation. The proximal tubule (PT), which is just upstream of the LOH and is a major site for Ca2+ reabsorption, could be a regulator of such CaP crystal formation. However, PT Ca2+ reabsorption is mostly described as being paracellular. Here, we show the existence of a regulated transcellular Ca2+ entry pathway in luminal membrane PT cells induced by Ca2+-sensing receptor (CSR, also known as CASR)-mediated activation of transient receptor potential canonical 3 (TRPC3) channels. In support of this idea, we found that both CSR and TRPC3 are physically and functionally coupled at the luminal membrane of PT cells. More importantly, TRPC3-deficient mice presented with a deficiency in PT Ca2+ entry/transport, elevated urinary [Ca2+], microcalcifications in LOH and urine microcrystals formations. Taken together, these data suggest that a signaling complex comprising CSR and TRPC3 exists in the PT and can mediate transcellular Ca2+ transport, which could be critical in maintaining the PT luminal [Ca2+] to mitigate formation of the CaP crystals in LOH and subsequent formation of calcium stones.
format Artículo
author Ibeh, Cliff Lawrence
Yiu, Allen J.
Kanaras, Yianni L.
Paal, Edina
Birnbaumer, Lutz
Jose, Pedro A.
Bandyopadhyay, Bidhan C.
author_facet Ibeh, Cliff Lawrence
Yiu, Allen J.
Kanaras, Yianni L.
Paal, Edina
Birnbaumer, Lutz
Jose, Pedro A.
Bandyopadhyay, Bidhan C.
author_sort Ibeh, Cliff Lawrence
title Evidence for a regulated Ca2+ entry in proximal tubular cells and its implication in calcium stone formation
title_short Evidence for a regulated Ca2+ entry in proximal tubular cells and its implication in calcium stone formation
title_full Evidence for a regulated Ca2+ entry in proximal tubular cells and its implication in calcium stone formation
title_fullStr Evidence for a regulated Ca2+ entry in proximal tubular cells and its implication in calcium stone formation
title_full_unstemmed Evidence for a regulated Ca2+ entry in proximal tubular cells and its implication in calcium stone formation
title_sort evidence for a regulated ca2+ entry in proximal tubular cells and its implication in calcium stone formation
publisher The Company of Biologists
publishDate 2020
url https://repositorio.uca.edu.ar/handle/123456789/9396
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