Oxygen-dependent hydroxylation by FIH regulates the TRPV3 ion channel

Sarah Karttunen, Michael Duffield, Nathan R. Scrimgeour, Lauren Squires, Wai Li Lim, Mark L. Dallas, Jason L. Scragg, Johana Chicher, Keyur A. Dave, Murray L. Whitelaw, Chris Peers, Jeffrey J. Gorman, Jonathan M. Gleadle, Grigori Y. Rychkov, Daniel J. Peet

Research output: Contribution to journalArticlepeer-review

30 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 languageEnglish
Pages (from-to)225-231
Number of pages7
JournalJournal of Cell Science
Volume128
Issue number2
DOIs
Publication statusPublished or Issued - 2015

Keywords

  • FIH
  • Hydroxylation
  • Hypoxia
  • TRPV3

ASJC Scopus subject areas

  • Cell Biology

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