The serum and glucocorticoid-inducible kinase SGK1 and the Na+/H+ exchange regulating factor NHERF2 synergize to stimulate the renal outer medullary K+ channel ROMK1

C. Chris Yun, Monica Palmada, Hamdy M. Embark, Olga Fedorenko, Yuxi Feng, Guido Henke, Iwan Setiawan, Christoph Boehmer, Edward J. Weinman, Sabrina Sandrasagra, Christoph Korbmacher, Philip Cohen, David Pearce, Florian Lang

Результат исследований: Материалы для журналаСтатья

116 Цитирования (Scopus)

Выдержка

Mineralocorticoids stimulate Na+ reabsorption and K+ secretion in principal cells of connecting tubule and collecting duct. The involved ion channels are ENaC and ROMK1, respectively. In Xenopus oocytes, the serum and glucocorticoid-sensitive kinase SGK1 has been shown to increase ENaC activity by enhancing its abundance in the plasma membrane. With the same method, ROMK1 appeared to be insensitive to regulation by SGK1. On the other hand, ROMK1 has been shown to colocalize with NHERF2, a protein mediating targeting and trafficking of transport proteins into the cell membrane. The present study has been performed to test whether NHERF2 is required for regulation of ROMK1 by SGK1. Coexpression of neither NHERF2 nor SGK1 with ROMK1 increases ROMK1 activity. However, coexpression of NHERF2 and SGK1 together with ROMK1 markedly increases K+ channel activity. The combined effect of SGK1 and NHERF2 does not significantly alter the I/V relation of the channel but increases the abundance of the channel in the membrane and decreases the decay of channel activity after inhibition of vesicle insertion with brefeldin. Coexpression of NHERF2 and SGK1 does not modify cytosolic pH but leads to a slight shift of pKa of ROMK1 to more acidic values. In conclusion, NHERF2 and SGK1 interact to enhance ROMK1 activity in large part by enhancing the abundance of channel protein within the cell membrane. This interaction allows the integration of genomic regulation and activation of SGK1 and NHERF2 in the control of ROMK1 activity and renal K+ excretion.

Язык оригиналаАнглийский
Страницы (с-по)2823-2830
Число страниц8
ЖурналJournal of the American Society of Nephrology
Том13
Номер выпуска12
DOI
СостояниеОпубликовано - дек 2002

Отпечаток

Protein Transport
Ion Channels
Glucocorticoids
Cell Membrane
Kidney
Mineralocorticoids
Xenopus
Oocytes
Carrier Proteins
Membrane Proteins
Phosphotransferases
Serum
serum-inducible kinase
Renal Elimination

ASJC Scopus subject areas

  • Nephrology

Цитировать

The serum and glucocorticoid-inducible kinase SGK1 and the Na+/H+ exchange regulating factor NHERF2 synergize to stimulate the renal outer medullary K+ channel ROMK1. / Yun, C. Chris; Palmada, Monica; Embark, Hamdy M.; Fedorenko, Olga; Feng, Yuxi; Henke, Guido; Setiawan, Iwan; Boehmer, Christoph; Weinman, Edward J.; Sandrasagra, Sabrina; Korbmacher, Christoph; Cohen, Philip; Pearce, David; Lang, Florian.

В: Journal of the American Society of Nephrology, Том 13, № 12, 12.2002, стр. 2823-2830.

Результат исследований: Материалы для журналаСтатья

Yun, CC, Palmada, M, Embark, HM, Fedorenko, O, Feng, Y, Henke, G, Setiawan, I, Boehmer, C, Weinman, EJ, Sandrasagra, S, Korbmacher, C, Cohen, P, Pearce, D & Lang, F 2002, 'The serum and glucocorticoid-inducible kinase SGK1 and the Na+/H+ exchange regulating factor NHERF2 synergize to stimulate the renal outer medullary K+ channel ROMK1', Journal of the American Society of Nephrology, том. 13, № 12, стр. 2823-2830. https://doi.org/10.1097/01.ASN.0000035085.54451.81
Yun, C. Chris ; Palmada, Monica ; Embark, Hamdy M. ; Fedorenko, Olga ; Feng, Yuxi ; Henke, Guido ; Setiawan, Iwan ; Boehmer, Christoph ; Weinman, Edward J. ; Sandrasagra, Sabrina ; Korbmacher, Christoph ; Cohen, Philip ; Pearce, David ; Lang, Florian. / The serum and glucocorticoid-inducible kinase SGK1 and the Na+/H+ exchange regulating factor NHERF2 synergize to stimulate the renal outer medullary K+ channel ROMK1. В: Journal of the American Society of Nephrology. 2002 ; Том 13, № 12. стр. 2823-2830.
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abstract = "Mineralocorticoids stimulate Na+ reabsorption and K+ secretion in principal cells of connecting tubule and collecting duct. The involved ion channels are ENaC and ROMK1, respectively. In Xenopus oocytes, the serum and glucocorticoid-sensitive kinase SGK1 has been shown to increase ENaC activity by enhancing its abundance in the plasma membrane. With the same method, ROMK1 appeared to be insensitive to regulation by SGK1. On the other hand, ROMK1 has been shown to colocalize with NHERF2, a protein mediating targeting and trafficking of transport proteins into the cell membrane. The present study has been performed to test whether NHERF2 is required for regulation of ROMK1 by SGK1. Coexpression of neither NHERF2 nor SGK1 with ROMK1 increases ROMK1 activity. However, coexpression of NHERF2 and SGK1 together with ROMK1 markedly increases K+ channel activity. The combined effect of SGK1 and NHERF2 does not significantly alter the I/V relation of the channel but increases the abundance of the channel in the membrane and decreases the decay of channel activity after inhibition of vesicle insertion with brefeldin. Coexpression of NHERF2 and SGK1 does not modify cytosolic pH but leads to a slight shift of pKa of ROMK1 to more acidic values. In conclusion, NHERF2 and SGK1 interact to enhance ROMK1 activity in large part by enhancing the abundance of channel protein within the cell membrane. This interaction allows the integration of genomic regulation and activation of SGK1 and NHERF2 in the control of ROMK1 activity and renal K+ excretion.",
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T1 - The serum and glucocorticoid-inducible kinase SGK1 and the Na+/H+ exchange regulating factor NHERF2 synergize to stimulate the renal outer medullary K+ channel ROMK1

AU - Yun, C. Chris

AU - Palmada, Monica

AU - Embark, Hamdy M.

AU - Fedorenko, Olga

AU - Feng, Yuxi

AU - Henke, Guido

AU - Setiawan, Iwan

AU - Boehmer, Christoph

AU - Weinman, Edward J.

AU - Sandrasagra, Sabrina

AU - Korbmacher, Christoph

AU - Cohen, Philip

AU - Pearce, David

AU - Lang, Florian

PY - 2002/12

Y1 - 2002/12

N2 - Mineralocorticoids stimulate Na+ reabsorption and K+ secretion in principal cells of connecting tubule and collecting duct. The involved ion channels are ENaC and ROMK1, respectively. In Xenopus oocytes, the serum and glucocorticoid-sensitive kinase SGK1 has been shown to increase ENaC activity by enhancing its abundance in the plasma membrane. With the same method, ROMK1 appeared to be insensitive to regulation by SGK1. On the other hand, ROMK1 has been shown to colocalize with NHERF2, a protein mediating targeting and trafficking of transport proteins into the cell membrane. The present study has been performed to test whether NHERF2 is required for regulation of ROMK1 by SGK1. Coexpression of neither NHERF2 nor SGK1 with ROMK1 increases ROMK1 activity. However, coexpression of NHERF2 and SGK1 together with ROMK1 markedly increases K+ channel activity. The combined effect of SGK1 and NHERF2 does not significantly alter the I/V relation of the channel but increases the abundance of the channel in the membrane and decreases the decay of channel activity after inhibition of vesicle insertion with brefeldin. Coexpression of NHERF2 and SGK1 does not modify cytosolic pH but leads to a slight shift of pKa of ROMK1 to more acidic values. In conclusion, NHERF2 and SGK1 interact to enhance ROMK1 activity in large part by enhancing the abundance of channel protein within the cell membrane. This interaction allows the integration of genomic regulation and activation of SGK1 and NHERF2 in the control of ROMK1 activity and renal K+ excretion.

AB - Mineralocorticoids stimulate Na+ reabsorption and K+ secretion in principal cells of connecting tubule and collecting duct. The involved ion channels are ENaC and ROMK1, respectively. In Xenopus oocytes, the serum and glucocorticoid-sensitive kinase SGK1 has been shown to increase ENaC activity by enhancing its abundance in the plasma membrane. With the same method, ROMK1 appeared to be insensitive to regulation by SGK1. On the other hand, ROMK1 has been shown to colocalize with NHERF2, a protein mediating targeting and trafficking of transport proteins into the cell membrane. The present study has been performed to test whether NHERF2 is required for regulation of ROMK1 by SGK1. Coexpression of neither NHERF2 nor SGK1 with ROMK1 increases ROMK1 activity. However, coexpression of NHERF2 and SGK1 together with ROMK1 markedly increases K+ channel activity. The combined effect of SGK1 and NHERF2 does not significantly alter the I/V relation of the channel but increases the abundance of the channel in the membrane and decreases the decay of channel activity after inhibition of vesicle insertion with brefeldin. Coexpression of NHERF2 and SGK1 does not modify cytosolic pH but leads to a slight shift of pKa of ROMK1 to more acidic values. In conclusion, NHERF2 and SGK1 interact to enhance ROMK1 activity in large part by enhancing the abundance of channel protein within the cell membrane. This interaction allows the integration of genomic regulation and activation of SGK1 and NHERF2 in the control of ROMK1 activity and renal K+ excretion.

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