Oxygen-dependent hydroxylation by Factor Inhibiting HIF (FIH) regulates the TRPV3 ion channel

Karttunen, S., Duffield, M., Scrimgeour, N. R., Squires, L., Lim, W. L., Dallas, M. L. ORCID: https://orcid.org/0000-0002-5190-0522, Scragg, J. L., Chicher, J., Dave, K. A., Whitelaw, M. L., Peers, C., Gorman, J. J., Gleadle, J. M., Rychkov, G. Y. and Peet, D. J. (2015) Oxygen-dependent hydroxylation by Factor Inhibiting HIF (FIH) regulates the TRPV3 ion channel. Journal of Cell Science, 128 (2). pp. 225-231. ISSN 0021-9533 doi: 10.1242/jcs.158451

Abstract/Summary

Factor Inhibiting HIF (FIH) is an oxygen-dependent asparaginyl hydroxylase that regulates the hypoxia-inducible factors (HIFs). Several proteins containing ankyrin repeat domains 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 ankyrin repeat domain. 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 oxygendependent asparaginyl hydroxylation is likely to extend to other ion channels.