γ-Adducin stimulates the thiazide-sensitive NaCl cotransporter

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γ-Adducin stimulates the thiazide-sensitive NaCl cotransporter. / Dimke, Henrik Anthony; San-Cristobal, Pedro; de Graaf, Mark; Lenders, Jacques W; Deinum, Jaap; Hoenderop, Joost G J; Bindels, René J M.

In: Journal of the American Society of Nephrology, Vol. 22, No. 3, 2011, p. 508-17.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Dimke, HA, San-Cristobal, P, de Graaf, M, Lenders, JW, Deinum, J, Hoenderop, JGJ & Bindels, RJM 2011, 'γ-Adducin stimulates the thiazide-sensitive NaCl cotransporter', Journal of the American Society of Nephrology, vol. 22, no. 3, pp. 508-17. https://doi.org/10.1681/ASN.2010060606

APA

Dimke, H. A., San-Cristobal, P., de Graaf, M., Lenders, J. W., Deinum, J., Hoenderop, J. G. J., & Bindels, R. J. M. (2011). γ-Adducin stimulates the thiazide-sensitive NaCl cotransporter. Journal of the American Society of Nephrology, 22(3), 508-17. https://doi.org/10.1681/ASN.2010060606

CBE

Dimke HA, San-Cristobal P, de Graaf M, Lenders JW, Deinum J, Hoenderop JGJ, Bindels RJM. 2011. γ-Adducin stimulates the thiazide-sensitive NaCl cotransporter. Journal of the American Society of Nephrology. 22(3):508-17. https://doi.org/10.1681/ASN.2010060606

MLA

Dimke, Henrik Anthony et al. "γ-Adducin stimulates the thiazide-sensitive NaCl cotransporter". Journal of the American Society of Nephrology. 2011, 22(3). 508-17. https://doi.org/10.1681/ASN.2010060606

Vancouver

Dimke HA, San-Cristobal P, de Graaf M, Lenders JW, Deinum J, Hoenderop JGJ et al. γ-Adducin stimulates the thiazide-sensitive NaCl cotransporter. Journal of the American Society of Nephrology. 2011;22(3):508-17. https://doi.org/10.1681/ASN.2010060606

Author

Dimke, Henrik Anthony ; San-Cristobal, Pedro ; de Graaf, Mark ; Lenders, Jacques W ; Deinum, Jaap ; Hoenderop, Joost G J ; Bindels, René J M. / γ-Adducin stimulates the thiazide-sensitive NaCl cotransporter. In: Journal of the American Society of Nephrology. 2011 ; Vol. 22, No. 3. pp. 508-17.

Bibtex

@article{8ec8964ff64e447b8fce969dfcc6322e,
title = "γ-Adducin stimulates the thiazide-sensitive NaCl cotransporter",
abstract = "The thiazide-sensitive NaCl cotransporter (NCC) plays a key role in renal salt reabsorption and the determination of systemic BP, but the molecular mechanisms governing the regulation of NCC are not completely understood. Here, through pull-down experiments coupled to mass spectrometry, we found that γ-adducin interacts with the NCC transporter. γ-Adducin colocalized with NCC to the distal convoluted tubule. (22)Na(+) uptake experiments in the Xenopus laevis oocyte showed that γ-adducin stimulated NCC activity in a dose-dependent manner, an effect that occurred upstream from With No Lysine (WNK) 4 kinase. The binding site of γ-adducin mapped to the N terminus of NCC and encompassed three previously reported phosphorylation sites. Supporting this site of interaction, competition with the N-terminal domain of NCC abolished the stimulatory effect of γ-adducin on the transporter. γ-Adducin failed to increase NCC activity when these phosphorylation sites were constitutively inactive or active. In addition, γ-adducin bound only to the dephosphorylated N terminus of NCC. Taken together, our observations suggest that γ-adducin dynamically regulates NCC, likely by amending the phosphorylation state, and consequently the activity, of the transporter. These data suggest that γ-adducin may influence BP homeostasis by modulating renal NaCl transport.",
keywords = "Absorption, Animals, Blood Pressure, Calmodulin-Binding Proteins, Dose-Response Relationship, Drug, Female, Humans, Kidney Tubules, Distal, Models, Animal, Oocytes, Phosphorylation, Sodium Chloride, Sodium Chloride Symporters, Xenopus laevis",
author = "Dimke, {Henrik Anthony} and Pedro San-Cristobal and {de Graaf}, Mark and Lenders, {Jacques W} and Jaap Deinum and Hoenderop, {Joost G J} and Bindels, {Ren{\'e} J M}",
year = "2011",
doi = "10.1681/ASN.2010060606",
language = "English",
volume = "22",
pages = "508--17",
journal = "Journal of the American Society of Nephrology",
issn = "1046-6673",
publisher = "The American Society of Nephrology",
number = "3",

}

RIS

TY - JOUR

T1 - γ-Adducin stimulates the thiazide-sensitive NaCl cotransporter

AU - Dimke, Henrik Anthony

AU - San-Cristobal, Pedro

AU - de Graaf, Mark

AU - Lenders, Jacques W

AU - Deinum, Jaap

AU - Hoenderop, Joost G J

AU - Bindels, René J M

PY - 2011

Y1 - 2011

N2 - The thiazide-sensitive NaCl cotransporter (NCC) plays a key role in renal salt reabsorption and the determination of systemic BP, but the molecular mechanisms governing the regulation of NCC are not completely understood. Here, through pull-down experiments coupled to mass spectrometry, we found that γ-adducin interacts with the NCC transporter. γ-Adducin colocalized with NCC to the distal convoluted tubule. (22)Na(+) uptake experiments in the Xenopus laevis oocyte showed that γ-adducin stimulated NCC activity in a dose-dependent manner, an effect that occurred upstream from With No Lysine (WNK) 4 kinase. The binding site of γ-adducin mapped to the N terminus of NCC and encompassed three previously reported phosphorylation sites. Supporting this site of interaction, competition with the N-terminal domain of NCC abolished the stimulatory effect of γ-adducin on the transporter. γ-Adducin failed to increase NCC activity when these phosphorylation sites were constitutively inactive or active. In addition, γ-adducin bound only to the dephosphorylated N terminus of NCC. Taken together, our observations suggest that γ-adducin dynamically regulates NCC, likely by amending the phosphorylation state, and consequently the activity, of the transporter. These data suggest that γ-adducin may influence BP homeostasis by modulating renal NaCl transport.

AB - The thiazide-sensitive NaCl cotransporter (NCC) plays a key role in renal salt reabsorption and the determination of systemic BP, but the molecular mechanisms governing the regulation of NCC are not completely understood. Here, through pull-down experiments coupled to mass spectrometry, we found that γ-adducin interacts with the NCC transporter. γ-Adducin colocalized with NCC to the distal convoluted tubule. (22)Na(+) uptake experiments in the Xenopus laevis oocyte showed that γ-adducin stimulated NCC activity in a dose-dependent manner, an effect that occurred upstream from With No Lysine (WNK) 4 kinase. The binding site of γ-adducin mapped to the N terminus of NCC and encompassed three previously reported phosphorylation sites. Supporting this site of interaction, competition with the N-terminal domain of NCC abolished the stimulatory effect of γ-adducin on the transporter. γ-Adducin failed to increase NCC activity when these phosphorylation sites were constitutively inactive or active. In addition, γ-adducin bound only to the dephosphorylated N terminus of NCC. Taken together, our observations suggest that γ-adducin dynamically regulates NCC, likely by amending the phosphorylation state, and consequently the activity, of the transporter. These data suggest that γ-adducin may influence BP homeostasis by modulating renal NaCl transport.

KW - Absorption

KW - Animals

KW - Blood Pressure

KW - Calmodulin-Binding Proteins

KW - Dose-Response Relationship, Drug

KW - Female

KW - Humans

KW - Kidney Tubules, Distal

KW - Models, Animal

KW - Oocytes

KW - Phosphorylation

KW - Sodium Chloride

KW - Sodium Chloride Symporters

KW - Xenopus laevis

U2 - 10.1681/ASN.2010060606

DO - 10.1681/ASN.2010060606

M3 - Journal article

C2 - 21164023

VL - 22

SP - 508

EP - 517

JO - Journal of the American Society of Nephrology

JF - Journal of the American Society of Nephrology

SN - 1046-6673

IS - 3

ER -