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 (Lead / Corresponding author)

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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.

    Original languageEnglish
    Pages (from-to)2823-2830
    Number of pages8
    JournalJournal of the American Society of Nephrology
    Volume13
    Issue number12
    DOIs
    Publication statusPublished - 1 Dec 2002

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

    Cite this

    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. In: Journal of the American Society of Nephrology. 2002 ; Vol. 13, No. 12. pp. 2823-2830.
    @article{934d5340de1249859c8add36647c1c14,
    title = "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",
    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.",
    author = "Yun, {C. Chris} and Monica Palmada and Embark, {Hamdy M.} and Olga Fedorenko and Yuxi Feng and Guido Henke and Iwan Setiawan and Christoph Boehmer and Weinman, {Edward J.} and Sabrina Sandrasagra and Christoph Korbmacher and Philip Cohen and David Pearce and Florian Lang",
    year = "2002",
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    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, vol. 13, no. 12, pp. 2823-2830. https://doi.org/10.1097/01.ASN.0000035085.54451.81

    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 (Lead / Corresponding author).

    In: Journal of the American Society of Nephrology, Vol. 13, No. 12, 01.12.2002, p. 2823-2830.

    Research output: Contribution to journalArticle

    TY - JOUR

    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 - 2002/12/1

    Y1 - 2002/12/1

    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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    JO - Journal of the American Society of Nephrology

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