Evidence for a regulated ca2+ entry in proximal tubular cells and its implication in calcium stone formation

Autores
Ibeh, Cliff Lawrence; Yiu, Allen J.; Kanaras, Yianni L.; Paal, Edina; Birnbaumer, Lutz; Jose, Pedro A.; Bandyopadhyay, Bidhan C.
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Ibeh, Cliff Lawrence. Veterans Affairs Medical Center; Estados Unidos
Fil: Yiu, Allen J.. Veterans Affairs Medical Center; Estados Unidos. The George Washington University; Estados Unidos
Fil: Kanaras, Yianni L.. Veterans Affairs Medical Center; Estados Unidos
Fil: Paal, Edina. Veterans Affairs Medical Center; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Jose, Pedro A.. The George Washington University; Estados Unidos
Fil: Bandyopadhyay, Bidhan C.. Veterans Affairs Medical Center; Estados Unidos. The George Washington University; Estados Unidos
Materia
CA2+ CHANNEL
CA2+ SIGNALING
CALCIUM PHOSPHATE STONE
LOOP OF HENLE
RENAL CALCIUM TRANSPORT
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/231323
Acceder
id CONICETDig_09fdb3ecc08ecdc55bb4de90022a5ff2
oai_identifier_str oai:ri.conicet.gov.ar:11336/231323
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Evidence for a regulated ca2+ entry in proximal tubular cells and its implication in calcium stone formationIbeh, Cliff LawrenceYiu, Allen J.Kanaras, Yianni L.Paal, EdinaBirnbaumer, LutzJose, Pedro A.Bandyopadhyay, Bidhan C.CA2+ CHANNELCA2+ SIGNALINGCALCIUM PHOSPHATE STONELOOP OF HENLERENAL CALCIUM TRANSPORThttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Calcium 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.Fil: Ibeh, Cliff Lawrence. Veterans Affairs Medical Center; Estados UnidosFil: Yiu, Allen J.. Veterans Affairs Medical Center; Estados Unidos. The George Washington University; Estados UnidosFil: Kanaras, Yianni L.. Veterans Affairs Medical Center; Estados UnidosFil: Paal, Edina. Veterans Affairs Medical Center; Estados UnidosFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Jose, Pedro A.. The George Washington University; Estados UnidosFil: Bandyopadhyay, Bidhan C.. Veterans Affairs Medical Center; Estados Unidos. The George Washington University; Estados UnidosCompany of Biologists2019-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/231323Ibeh, Cliff Lawrence; Yiu, Allen J.; Kanaras, Yianni L.; Paal, Edina; Birnbaumer, Lutz; et al.; Evidence for a regulated ca2+ entry in proximal tubular cells and its implication in calcium stone formation; Company of Biologists; Journal of Cell Science; 132; 9; 5-2019; 1-170021-95331477-9137CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1242/jcs.225268info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:48:06Zoai:ri.conicet.gov.ar:11336/231323instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:48:06.529CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Evidence for a regulated ca2+ entry in proximal tubular cells and its implication in calcium stone formation
title Evidence for a regulated ca2+ entry in proximal tubular cells and its implication in calcium stone formation
spellingShingle Evidence for a regulated ca2+ entry in proximal tubular cells and its implication in calcium stone formation
Ibeh, Cliff Lawrence
CA2+ CHANNEL
CA2+ SIGNALING
CALCIUM PHOSPHATE STONE
LOOP OF HENLE
RENAL CALCIUM TRANSPORT
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
dc.creator.none.fl_str_mv Ibeh, Cliff Lawrence
Yiu, Allen J.
Kanaras, Yianni L.
Paal, Edina
Birnbaumer, Lutz
Jose, Pedro A.
Bandyopadhyay, Bidhan C.
author Ibeh, Cliff Lawrence
author_facet Ibeh, Cliff Lawrence
Yiu, Allen J.
Kanaras, Yianni L.
Paal, Edina
Birnbaumer, Lutz
Jose, Pedro A.
Bandyopadhyay, Bidhan C.
author_role author
author2 Yiu, Allen J.
Kanaras, Yianni L.
Paal, Edina
Birnbaumer, Lutz
Jose, Pedro A.
Bandyopadhyay, Bidhan C.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv CA2+ CHANNEL
CA2+ SIGNALING
CALCIUM PHOSPHATE STONE
LOOP OF HENLE
RENAL CALCIUM TRANSPORT
topic CA2+ CHANNEL
CA2+ SIGNALING
CALCIUM PHOSPHATE STONE
LOOP OF HENLE
RENAL CALCIUM TRANSPORT
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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.
Fil: Ibeh, Cliff Lawrence. Veterans Affairs Medical Center; Estados Unidos
Fil: Yiu, Allen J.. Veterans Affairs Medical Center; Estados Unidos. The George Washington University; Estados Unidos
Fil: Kanaras, Yianni L.. Veterans Affairs Medical Center; Estados Unidos
Fil: Paal, Edina. Veterans Affairs Medical Center; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Jose, Pedro A.. The George Washington University; Estados Unidos
Fil: Bandyopadhyay, Bidhan C.. Veterans Affairs Medical Center; Estados Unidos. The George Washington University; Estados Unidos
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/231323
Ibeh, Cliff Lawrence; Yiu, Allen J.; Kanaras, Yianni L.; Paal, Edina; Birnbaumer, Lutz; et al.; Evidence for a regulated ca2+ entry in proximal tubular cells and its implication in calcium stone formation; Company of Biologists; Journal of Cell Science; 132; 9; 5-2019; 1-17
0021-9533
1477-9137
CONICET Digital
CONICET
url http://hdl.handle.net/11336/231323
identifier_str_mv Ibeh, Cliff Lawrence; Yiu, Allen J.; Kanaras, Yianni L.; Paal, Edina; Birnbaumer, Lutz; et al.; Evidence for a regulated ca2+ entry in proximal tubular cells and its implication in calcium stone formation; Company of Biologists; Journal of Cell Science; 132; 9; 5-2019; 1-17
0021-9533
1477-9137
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1242/jcs.225268
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Company of Biologists
publisher.none.fl_str_mv Company of Biologists
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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