Research ArticleCELL BIOLOGY

A persulfidation-based mechanism controls aquaporin-8 conductance

See allHide authors and affiliations

Science Advances  02 May 2018:
Vol. 4, no. 5, eaar5770
DOI: 10.1126/sciadv.aar5770

You are currently viewing the abstract.

View Full Text

Abstract

Upon engagement of tyrosine kinase receptors, nicotinamide adenine dinucleotide phosphate (NADPH)–oxidases release H2O2 in the extracellular space. We reported previously that aquaporin-8 (AQP8) transports H2O2 across the plasma membrane and is reversibly gated during cell stress, modulating signal strength and duration. We show that AQP8 gating is mediated by persulfidation of cysteine 53 (C53). Treatment with H2S is sufficient to block H2O2 entry in unstressed cells. Silencing cystathionine β-synthase (CBS) prevents closure, suggesting that this enzyme is the main source of H2S. Molecular modeling indicates that C53 persulfidation displaces a nearby histidine located in the narrowest part of the channel. We propose that H2O2 molecules transported through AQP8 sulfenylate C53, making it susceptible to H2S produced by CBS. This mechanism tunes H2O2 transport and may control signaling and limit oxidative stress.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

View Full Text