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SORLA/SORL1 functionally interacts with SPAK to control renal activation of Na+-K+-Cl- cotransporter 2

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SORLA/SORL1 functionally interacts with SPAK to control renal activation of Na+-K+-Cl- cotransporter 2. / Reiche, Juliane; Theilig, Franziska; Rafiqi, Fatema H.; Carlo, Anne-Sophie; Militz, Daniel; Mutig, Kerim; Todiras, Mihail; Christensen, Erik Ilso; Ellison, David H.; Bader, Michael; Nykjaer, Anders; Bachmann, Sebastian; Alessi, Dario; Willnow, Thomas E.

In: Molecular and Cellular Biology, Vol. 30, No. 12, 15.06.2010, p. 3027-3037.

Research output: Contribution to journalArticle

Harvard

Reiche, J, Theilig, F, Rafiqi, FH, Carlo, A-S, Militz, D, Mutig, K, Todiras, M, Christensen, EI, Ellison, DH, Bader, M, Nykjaer, A, Bachmann, S, Alessi, D & Willnow, TE 2010, 'SORLA/SORL1 functionally interacts with SPAK to control renal activation of Na+-K+-Cl- cotransporter 2' Molecular and Cellular Biology, vol 30, no. 12, pp. 3027-3037.

APA

Reiche, J., Theilig, F., Rafiqi, F. H., Carlo, A-S., Militz, D., Mutig, K., Todiras, M., Christensen, E. I., Ellison, D. H., Bader, M., Nykjaer, A., Bachmann, S., Alessi, D., & Willnow, T. E. (2010). SORLA/SORL1 functionally interacts with SPAK to control renal activation of Na+-K+-Cl- cotransporter 2. Molecular and Cellular Biology, 30(12), 3027-3037doi: 10.1128/MCB.01560-09

Vancouver

Reiche J, Theilig F, Rafiqi FH, Carlo A-S, Militz D, Mutig K et al. SORLA/SORL1 functionally interacts with SPAK to control renal activation of Na+-K+-Cl- cotransporter 2. Molecular and Cellular Biology. 2010 Jun 15;30(12):3027-3037.

Author

Reiche, Juliane; Theilig, Franziska; Rafiqi, Fatema H.; Carlo, Anne-Sophie; Militz, Daniel; Mutig, Kerim; Todiras, Mihail; Christensen, Erik Ilso; Ellison, David H.; Bader, Michael; Nykjaer, Anders; Bachmann, Sebastian; Alessi, Dario; Willnow, Thomas E. / SORLA/SORL1 functionally interacts with SPAK to control renal activation of Na+-K+-Cl- cotransporter 2.

In: Molecular and Cellular Biology, Vol. 30, No. 12, 15.06.2010, p. 3027-3037.

Research output: Contribution to journalArticle

Bibtex - Download

@article{abc7e6f3899f496a9d67c3b2c2913bac,
title = "SORLA/SORL1 functionally interacts with SPAK to control renal activation of Na+-K+-Cl- cotransporter 2",
author = "Juliane Reiche and Franziska Theilig and Rafiqi, {Fatema H.} and Anne-Sophie Carlo and Daniel Militz and Kerim Mutig and Mihail Todiras and Christensen, {Erik Ilso} and Ellison, {David H.} and Michael Bader and Anders Nykjaer and Sebastian Bachmann and Dario Alessi and Willnow, {Thomas E.}",
year = "2010",
volume = "30",
number = "12",
pages = "3027--3037",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - SORLA/SORL1 functionally interacts with SPAK to control renal activation of Na+-K+-Cl- cotransporter 2

A1 - Reiche,Juliane

A1 - Theilig,Franziska

A1 - Rafiqi,Fatema H.

A1 - Carlo,Anne-Sophie

A1 - Militz,Daniel

A1 - Mutig,Kerim

A1 - Todiras,Mihail

A1 - Christensen,Erik Ilso

A1 - Ellison,David H.

A1 - Bader,Michael

A1 - Nykjaer,Anders

A1 - Bachmann,Sebastian

A1 - Alessi,Dario

A1 - Willnow,Thomas E.

AU - Reiche,Juliane

AU - Theilig,Franziska

AU - Rafiqi,Fatema H.

AU - Carlo,Anne-Sophie

AU - Militz,Daniel

AU - Mutig,Kerim

AU - Todiras,Mihail

AU - Christensen,Erik Ilso

AU - Ellison,David H.

AU - Bader,Michael

AU - Nykjaer,Anders

AU - Bachmann,Sebastian

AU - Alessi,Dario

AU - Willnow,Thomas E.

PY - 2010/6/15

Y1 - 2010/6/15

N2 - <p>Proper control of NaCl excretion in the kidney is central to bodily functions, yet many mechanisms that regulate reabsorption of sodium and chloride in the kidney remain incompletely understood. Here, we identify an important role played by the intracellular sorting receptor SORLA (sorting protein-related receptor with A-type repeats) in functional activation of renal ion transporters. We demonstrate that SORLA is expressed in epithelial cells of the thick ascending limb (TAL) of Henle's loop and that lack of receptor expression in this cell type in SORLA-deficient mice results in an inability to properly reabsorb sodium and chloride during osmotic stress. The underlying cellular defect was correlated with an inability of the TAL to phosphorylate Na+-K+-Cl- cotransporter 2 (NKCC2), the major sodium transporter in the distal nephron. SORLA functionally interacts with Ste-20-related proline-alanine-rich kinase (SPAK), an activator of NKCC2, and receptor deficiency is associated with missorting of SPAK. Our data suggest a novel regulatory pathway whereby intracellular trafficking of SPAK by the sorting receptor SORLA is crucial for proper NKCC2 activation and for maintenance of renal ion balance.</p>

AB - <p>Proper control of NaCl excretion in the kidney is central to bodily functions, yet many mechanisms that regulate reabsorption of sodium and chloride in the kidney remain incompletely understood. Here, we identify an important role played by the intracellular sorting receptor SORLA (sorting protein-related receptor with A-type repeats) in functional activation of renal ion transporters. We demonstrate that SORLA is expressed in epithelial cells of the thick ascending limb (TAL) of Henle's loop and that lack of receptor expression in this cell type in SORLA-deficient mice results in an inability to properly reabsorb sodium and chloride during osmotic stress. The underlying cellular defect was correlated with an inability of the TAL to phosphorylate Na+-K+-Cl- cotransporter 2 (NKCC2), the major sodium transporter in the distal nephron. SORLA functionally interacts with Ste-20-related proline-alanine-rich kinase (SPAK), an activator of NKCC2, and receptor deficiency is associated with missorting of SPAK. Our data suggest a novel regulatory pathway whereby intracellular trafficking of SPAK by the sorting receptor SORLA is crucial for proper NKCC2 activation and for maintenance of renal ion balance.</p>

U2 - 10.1128/MCB.01560-09

DO - 10.1128/MCB.01560-09

M1 - Article

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 12

VL - 30

SP - 3027

EP - 3037

ER -

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