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Single point mutations of aromatic residues in transmembrane helices 5 and -6 differentially affect TRPV4 activation by 4α-PDD and hypotonicity: implications for the role of the pore region in regulating TRPV4 activity

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Standard

Single point mutations of aromatic residues in transmembrane helices 5 and -6 differentially affect TRPV4 activation by 4α-PDD and hypotonicity : implications for the role of the pore region in regulating TRPV4 activity. / Klausen, Thomas Kjær; Janssens, Annelies; Prenen, Jean; Owsianik, Grzegorz; Hoffmann, Else Kay; Pedersen, Stine Helene Falsig; Nilius, Bernd.

I: Cell Calcium, Bind 55, Nr. 1, 2014, s. 38-47.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Klausen, TK, Janssens, A, Prenen, J, Owsianik, G, Hoffmann, EK, Pedersen, SHF & Nilius, B 2014, 'Single point mutations of aromatic residues in transmembrane helices 5 and -6 differentially affect TRPV4 activation by 4α-PDD and hypotonicity: implications for the role of the pore region in regulating TRPV4 activity', Cell Calcium, bind 55, nr. 1, s. 38-47. https://doi.org/10.1016/j.ceca.2013.11.001

APA

Klausen, T. K., Janssens, A., Prenen, J., Owsianik, G., Hoffmann, E. K., Pedersen, S. H. F., & Nilius, B. (2014). Single point mutations of aromatic residues in transmembrane helices 5 and -6 differentially affect TRPV4 activation by 4α-PDD and hypotonicity: implications for the role of the pore region in regulating TRPV4 activity. Cell Calcium, 55(1), 38-47. https://doi.org/10.1016/j.ceca.2013.11.001

Vancouver

Klausen TK, Janssens A, Prenen J, Owsianik G, Hoffmann EK, Pedersen SHF o.a. Single point mutations of aromatic residues in transmembrane helices 5 and -6 differentially affect TRPV4 activation by 4α-PDD and hypotonicity: implications for the role of the pore region in regulating TRPV4 activity. Cell Calcium. 2014;55(1):38-47. https://doi.org/10.1016/j.ceca.2013.11.001

Author

Klausen, Thomas Kjær ; Janssens, Annelies ; Prenen, Jean ; Owsianik, Grzegorz ; Hoffmann, Else Kay ; Pedersen, Stine Helene Falsig ; Nilius, Bernd. / Single point mutations of aromatic residues in transmembrane helices 5 and -6 differentially affect TRPV4 activation by 4α-PDD and hypotonicity : implications for the role of the pore region in regulating TRPV4 activity. I: Cell Calcium. 2014 ; Bind 55, Nr. 1. s. 38-47.

Bibtex

@article{e2a32c9b81a24ec29f468bf6d2727627,
title = "Single point mutations of aromatic residues in transmembrane helices 5 and -6 differentially affect TRPV4 activation by 4α-PDD and hypotonicity: implications for the role of the pore region in regulating TRPV4 activity",
abstract = "The importance of the TRPV4 channel for human physiology has been highlighted in recent years with the identification of an increasing number of hereditary diseases associated with mutations of this channel. However, the functional understanding of TRPV4 associated pathologies remains a puzzle due to incomplete understanding of the polymodal regulation of TRPV4 channels and lack of insight into the structure-function relationship of the channel. In this work, we identified a series of highly conserved aromatic residues in transmembrane (TM) helices 5-6 with profound importance for TRPV4 activity. Substituting F617, Y621 or F624 in TM5 with leucine reduced channel sensitivity to the agonist 4α-PDD and heat, yet two of these mutants - F617L and Y621L - showed increased activation in response to cell swelling. In TM6, a Y702L mutation significantly reduced sensitivity to all of the above stimuli. In conclusion, we have identified residues in TM5-6 which differentially affect heat and agonist activation, and we have demonstrated distinct activation pathways for 4α-PDD and osmolarity.",
author = "Klausen, {Thomas Kj{\ae}r} and Annelies Janssens and Jean Prenen and Grzegorz Owsianik and Hoffmann, {Else Kay} and Pedersen, {Stine Helene Falsig} and Bernd Nilius",
note = "Copyright {\textcopyright} 2013 Elsevier Ltd. All rights reserved.",
year = "2014",
doi = "10.1016/j.ceca.2013.11.001",
language = "English",
volume = "55",
pages = "38--47",
journal = "Cell Calcium",
issn = "0143-4160",
publisher = "Churchill Livingstone",
number = "1",

}

RIS

TY - JOUR

T1 - Single point mutations of aromatic residues in transmembrane helices 5 and -6 differentially affect TRPV4 activation by 4α-PDD and hypotonicity

T2 - implications for the role of the pore region in regulating TRPV4 activity

AU - Klausen, Thomas Kjær

AU - Janssens, Annelies

AU - Prenen, Jean

AU - Owsianik, Grzegorz

AU - Hoffmann, Else Kay

AU - Pedersen, Stine Helene Falsig

AU - Nilius, Bernd

N1 - Copyright © 2013 Elsevier Ltd. All rights reserved.

PY - 2014

Y1 - 2014

N2 - The importance of the TRPV4 channel for human physiology has been highlighted in recent years with the identification of an increasing number of hereditary diseases associated with mutations of this channel. However, the functional understanding of TRPV4 associated pathologies remains a puzzle due to incomplete understanding of the polymodal regulation of TRPV4 channels and lack of insight into the structure-function relationship of the channel. In this work, we identified a series of highly conserved aromatic residues in transmembrane (TM) helices 5-6 with profound importance for TRPV4 activity. Substituting F617, Y621 or F624 in TM5 with leucine reduced channel sensitivity to the agonist 4α-PDD and heat, yet two of these mutants - F617L and Y621L - showed increased activation in response to cell swelling. In TM6, a Y702L mutation significantly reduced sensitivity to all of the above stimuli. In conclusion, we have identified residues in TM5-6 which differentially affect heat and agonist activation, and we have demonstrated distinct activation pathways for 4α-PDD and osmolarity.

AB - The importance of the TRPV4 channel for human physiology has been highlighted in recent years with the identification of an increasing number of hereditary diseases associated with mutations of this channel. However, the functional understanding of TRPV4 associated pathologies remains a puzzle due to incomplete understanding of the polymodal regulation of TRPV4 channels and lack of insight into the structure-function relationship of the channel. In this work, we identified a series of highly conserved aromatic residues in transmembrane (TM) helices 5-6 with profound importance for TRPV4 activity. Substituting F617, Y621 or F624 in TM5 with leucine reduced channel sensitivity to the agonist 4α-PDD and heat, yet two of these mutants - F617L and Y621L - showed increased activation in response to cell swelling. In TM6, a Y702L mutation significantly reduced sensitivity to all of the above stimuli. In conclusion, we have identified residues in TM5-6 which differentially affect heat and agonist activation, and we have demonstrated distinct activation pathways for 4α-PDD and osmolarity.

U2 - 10.1016/j.ceca.2013.11.001

DO - 10.1016/j.ceca.2013.11.001

M3 - Journal article

C2 - 24342753

VL - 55

SP - 38

EP - 47

JO - Cell Calcium

JF - Cell Calcium

SN - 0143-4160

IS - 1

ER -

ID: 96480437