Oxygen-dependent hydroxylation by FIH regulates the TRPV3 ion channel

S Karttunen; M Duffield; Nathan Scrimgeour; L Squires; W Lim; M Dallas; J Scragg; J Chicher; K Dave; M Whitelaw; C Peers; J Gorman; Jonathan Gleadle; Grigori Rychkov; Daniel Peet

doi:10.1242/jcs.158451

Oxygen-dependent hydroxylation by FIH regulates the TRPV3 ion channel

S Karttunen, M Duffield, Nathan Scrimgeour, L Squires, W Lim, M Dallas, J Scragg, J Chicher, K Dave, M Whitelaw, C Peers, J Gorman, Jonathan Gleadle, Grigori Rychkov, Daniel Peet

Research output: Contribution to journal › Article › peer-review

37 Citations (Scopus)

Abstract

Factor inhibiting HIF (FIH, also known as HIF1AN) is an oxygendependent asparaginyl hydroxylase that regulates the hypoxiainducible factors (HIFs). Several proteins containing ankyrin repeat domains (ARDs) have been characterised as substrates of FIH, although there is little evidence for a functional consequence of hydroxylation on these substrates. This study demonstrates that the transient receptor potential vanilloid 3 (TRPV3) channel is hydroxylated by FIH on asparagine 242 within the cytoplasmic ARD. Hypoxia, FIH inhibitors and mutation of asparagine 242 all potentiated TRPV3-mediated current, without altering TRPV3 protein levels, indicating that oxygen-dependent hydroxylation inhibits TRPV3 activity. This novel mechanism of channel regulation by oxygen-dependent asparaginyl hydroxylation is likely to extend to other ion channels.

Original language	English
Pages (from-to)	225-231
Number of pages	7
Journal	Journal of Cell Science
Volume	128
Issue number	2
DOIs	https://doi.org/10.1242/jcs.158451
Publication status	Published - 2015

Keywords

FIH
Hydroxylation
Hypoxia
TRPV3

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10.1242/jcs.158451

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title = "Oxygen-dependent hydroxylation by FIH regulates the TRPV3 ion channel",

abstract = "Factor inhibiting HIF (FIH, also known as HIF1AN) is an oxygendependent asparaginyl hydroxylase that regulates the hypoxiainducible factors (HIFs). Several proteins containing ankyrin repeat domains (ARDs) have been characterised as substrates of FIH, although there is little evidence for a functional consequence of hydroxylation on these substrates. This study demonstrates that the transient receptor potential vanilloid 3 (TRPV3) channel is hydroxylated by FIH on asparagine 242 within the cytoplasmic ARD. Hypoxia, FIH inhibitors and mutation of asparagine 242 all potentiated TRPV3-mediated current, without altering TRPV3 protein levels, indicating that oxygen-dependent hydroxylation inhibits TRPV3 activity. This novel mechanism of channel regulation by oxygen-dependent asparaginyl hydroxylation is likely to extend to other ion channels.",

keywords = "FIH, Hydroxylation, Hypoxia, TRPV3",

author = "S Karttunen and M Duffield and Nathan Scrimgeour and L Squires and W Lim and M Dallas and J Scragg and J Chicher and K Dave and M Whitelaw and C Peers and J Gorman and Jonathan Gleadle and Grigori Rychkov and Daniel Peet",

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doi = "10.1242/jcs.158451",

language = "English",

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journal = "Journal of Cell Science",

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TY - JOUR

T1 - Oxygen-dependent hydroxylation by FIH regulates the TRPV3 ion channel

AU - Karttunen, S

AU - Duffield, M

AU - Scrimgeour, Nathan

AU - Squires, L

AU - Lim, W

AU - Dallas, M

AU - Scragg, J

AU - Chicher, J

AU - Dave, K

AU - Whitelaw, M

AU - Peers, C

AU - Gorman, J

AU - Gleadle, Jonathan

AU - Rychkov, Grigori

AU - Peet, Daniel

PY - 2015

Y1 - 2015

N2 - Factor inhibiting HIF (FIH, also known as HIF1AN) is an oxygendependent asparaginyl hydroxylase that regulates the hypoxiainducible factors (HIFs). Several proteins containing ankyrin repeat domains (ARDs) have been characterised as substrates of FIH, although there is little evidence for a functional consequence of hydroxylation on these substrates. This study demonstrates that the transient receptor potential vanilloid 3 (TRPV3) channel is hydroxylated by FIH on asparagine 242 within the cytoplasmic ARD. Hypoxia, FIH inhibitors and mutation of asparagine 242 all potentiated TRPV3-mediated current, without altering TRPV3 protein levels, indicating that oxygen-dependent hydroxylation inhibits TRPV3 activity. This novel mechanism of channel regulation by oxygen-dependent asparaginyl hydroxylation is likely to extend to other ion channels.

AB - Factor inhibiting HIF (FIH, also known as HIF1AN) is an oxygendependent asparaginyl hydroxylase that regulates the hypoxiainducible factors (HIFs). Several proteins containing ankyrin repeat domains (ARDs) have been characterised as substrates of FIH, although there is little evidence for a functional consequence of hydroxylation on these substrates. This study demonstrates that the transient receptor potential vanilloid 3 (TRPV3) channel is hydroxylated by FIH on asparagine 242 within the cytoplasmic ARD. Hypoxia, FIH inhibitors and mutation of asparagine 242 all potentiated TRPV3-mediated current, without altering TRPV3 protein levels, indicating that oxygen-dependent hydroxylation inhibits TRPV3 activity. This novel mechanism of channel regulation by oxygen-dependent asparaginyl hydroxylation is likely to extend to other ion channels.

KW - FIH

KW - Hydroxylation

KW - Hypoxia

KW - TRPV3

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U2 - 10.1242/jcs.158451

DO - 10.1242/jcs.158451

M3 - Article

SN - 0021-9533

VL - 128

SP - 225

EP - 231

JO - Journal of Cell Science

JF - Journal of Cell Science

IS - 2

ER -

Oxygen-dependent hydroxylation by FIH regulates the TRPV3 ion channel

Abstract

Keywords

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