Control of PTH secretion by the TRPC1 ion channel

Research output: Contribution to journalArticlepeer-review

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Control of PTH secretion by the TRPC1 ion channel. / Onopiuk, Marta; Eby, Bonnie; Nesin, Vasyl; Ngo, Peter; Lerner, Megan; Gorvin, Caroline M; Stokes, Victoria J; Thakker, Rajesh V; Brandi, Maria Luisa; Chang, Wenhan; Humphrey, Mary Beth; Tsiokas, Leonidas; Lau, Kai.

In: JCI Insight, Vol. 5, No. 8, 23.04.2020, p. 1-17.

Research output: Contribution to journalArticlepeer-review

Harvard

Onopiuk, M, Eby, B, Nesin, V, Ngo, P, Lerner, M, Gorvin, CM, Stokes, VJ, Thakker, RV, Brandi, ML, Chang, W, Humphrey, MB, Tsiokas, L & Lau, K 2020, 'Control of PTH secretion by the TRPC1 ion channel', JCI Insight, vol. 5, no. 8, pp. 1-17. https://doi.org/10.1172/jci.insight.132496

APA

Onopiuk, M., Eby, B., Nesin, V., Ngo, P., Lerner, M., Gorvin, C. M., Stokes, V. J., Thakker, R. V., Brandi, M. L., Chang, W., Humphrey, M. B., Tsiokas, L., & Lau, K. (2020). Control of PTH secretion by the TRPC1 ion channel. JCI Insight, 5(8), 1-17. https://doi.org/10.1172/jci.insight.132496

Vancouver

Onopiuk M, Eby B, Nesin V, Ngo P, Lerner M, Gorvin CM et al. Control of PTH secretion by the TRPC1 ion channel. JCI Insight. 2020 Apr 23;5(8):1-17. https://doi.org/10.1172/jci.insight.132496

Author

Onopiuk, Marta ; Eby, Bonnie ; Nesin, Vasyl ; Ngo, Peter ; Lerner, Megan ; Gorvin, Caroline M ; Stokes, Victoria J ; Thakker, Rajesh V ; Brandi, Maria Luisa ; Chang, Wenhan ; Humphrey, Mary Beth ; Tsiokas, Leonidas ; Lau, Kai. / Control of PTH secretion by the TRPC1 ion channel. In: JCI Insight. 2020 ; Vol. 5, No. 8. pp. 1-17.

Bibtex

@article{3fe690b830a249b28d59cd26b933d522,
title = "Control of PTH secretion by the TRPC1 ion channel",
abstract = "Familial hypocalciuric hypercalcemia (FHH) is a genetic condition associated with hypocalciuria, hypercalcemia, and, in some cases, inappropriately high levels of circulating parathyroid hormone (PTH). FHH is associated with inactivating mutations in the gene encoding the Ca2+-sensing receptor (CaSR), a GPCR, and GNA11 encoding G protein subunit α 11 (Gα11), implicating defective GPCR signaling as the root pathophysiology for FHH. However, the downstream mechanism by which CaSR activation inhibits PTH production/secretion is incompletely understood. Here, we show that mice lacking the transient receptor potential canonical channel 1 (TRPC1) develop chronic hypercalcemia, hypocalciuria, and elevated PTH levels, mimicking human FHH. Ex vivo and in vitro studies revealed that TRPC1 serves a necessary and sufficient mediator to suppress PTH secretion from parathyroid glands (PTGs) downstream of CaSR in response to high extracellular Ca2+ concentration. Gα11 physically interacted with both the N- and C-termini of TRPC1 and enhanced CaSR-induced TRPC1 activity in transfected cells. These data identify TRPC1-mediated Ca2+ signaling as an essential component of the cellular apparatus controlling PTH secretion in the PTG downstream of CaSR.",
author = "Marta Onopiuk and Bonnie Eby and Vasyl Nesin and Peter Ngo and Megan Lerner and Gorvin, {Caroline M} and Stokes, {Victoria J} and Thakker, {Rajesh V} and Brandi, {Maria Luisa} and Wenhan Chang and Humphrey, {Mary Beth} and Leonidas Tsiokas and Kai Lau",
year = "2020",
month = apr,
day = "23",
doi = "10.1172/jci.insight.132496",
language = "English",
volume = "5",
pages = "1--17",
journal = "JCI Insight",
issn = "2379-3708",
publisher = "American Society for Clinical Investigation",
number = "8",

}

RIS

TY - JOUR

T1 - Control of PTH secretion by the TRPC1 ion channel

AU - Onopiuk, Marta

AU - Eby, Bonnie

AU - Nesin, Vasyl

AU - Ngo, Peter

AU - Lerner, Megan

AU - Gorvin, Caroline M

AU - Stokes, Victoria J

AU - Thakker, Rajesh V

AU - Brandi, Maria Luisa

AU - Chang, Wenhan

AU - Humphrey, Mary Beth

AU - Tsiokas, Leonidas

AU - Lau, Kai

PY - 2020/4/23

Y1 - 2020/4/23

N2 - Familial hypocalciuric hypercalcemia (FHH) is a genetic condition associated with hypocalciuria, hypercalcemia, and, in some cases, inappropriately high levels of circulating parathyroid hormone (PTH). FHH is associated with inactivating mutations in the gene encoding the Ca2+-sensing receptor (CaSR), a GPCR, and GNA11 encoding G protein subunit α 11 (Gα11), implicating defective GPCR signaling as the root pathophysiology for FHH. However, the downstream mechanism by which CaSR activation inhibits PTH production/secretion is incompletely understood. Here, we show that mice lacking the transient receptor potential canonical channel 1 (TRPC1) develop chronic hypercalcemia, hypocalciuria, and elevated PTH levels, mimicking human FHH. Ex vivo and in vitro studies revealed that TRPC1 serves a necessary and sufficient mediator to suppress PTH secretion from parathyroid glands (PTGs) downstream of CaSR in response to high extracellular Ca2+ concentration. Gα11 physically interacted with both the N- and C-termini of TRPC1 and enhanced CaSR-induced TRPC1 activity in transfected cells. These data identify TRPC1-mediated Ca2+ signaling as an essential component of the cellular apparatus controlling PTH secretion in the PTG downstream of CaSR.

AB - Familial hypocalciuric hypercalcemia (FHH) is a genetic condition associated with hypocalciuria, hypercalcemia, and, in some cases, inappropriately high levels of circulating parathyroid hormone (PTH). FHH is associated with inactivating mutations in the gene encoding the Ca2+-sensing receptor (CaSR), a GPCR, and GNA11 encoding G protein subunit α 11 (Gα11), implicating defective GPCR signaling as the root pathophysiology for FHH. However, the downstream mechanism by which CaSR activation inhibits PTH production/secretion is incompletely understood. Here, we show that mice lacking the transient receptor potential canonical channel 1 (TRPC1) develop chronic hypercalcemia, hypocalciuria, and elevated PTH levels, mimicking human FHH. Ex vivo and in vitro studies revealed that TRPC1 serves a necessary and sufficient mediator to suppress PTH secretion from parathyroid glands (PTGs) downstream of CaSR in response to high extracellular Ca2+ concentration. Gα11 physically interacted with both the N- and C-termini of TRPC1 and enhanced CaSR-induced TRPC1 activity in transfected cells. These data identify TRPC1-mediated Ca2+ signaling as an essential component of the cellular apparatus controlling PTH secretion in the PTG downstream of CaSR.

U2 - 10.1172/jci.insight.132496

DO - 10.1172/jci.insight.132496

M3 - Article

C2 - 32213715

VL - 5

SP - 1

EP - 17

JO - JCI Insight

JF - JCI Insight

SN - 2379-3708

IS - 8

ER -