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 journalArticlepeer-review

    26 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 - 2015

    Keywords

    • FIH
    • Hydroxylation
    • Hypoxia
    • TRPV3

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