Publication details for Professor Martin CannMeigh, L., Greenhalgh, S.A., Rodgers, T.L., Cann, M.J., Roper, D.I. & Dale, N. (2013). CO2 directly modulates connexin 26 by formation of carbamate bridges between subunits. eLife 2: e01213.
- Publication type: Journal Article
- ISSN/ISBN: 2050-084X (electronic)
- DOI: 10.7554/eLife.01213
- Further publication details on publisher web site
- Durham Research Online (DRO) - may include full text
Author(s) from Durham
Homeostatic regulation of the partial pressure of CO2 (PCO2) is vital for life. Sensing of pH has been proposed as a sufficient proxy for determination of PCO2 and direct CO2-sensing largely discounted. Here we show that connexin 26 (Cx26) hemichannels, causally linked to respiratory chemosensitivity, are directly modulated by CO2. A ‘carbamylation motif’, present in CO2-sensitive connexins (Cx26, Cx30, Cx32) but absent from a CO2-insensitive connexin (Cx31), comprises Lys125 and four further amino acids that orient Lys125 towards Arg104 of the adjacent subunit of the connexin hexamer. Introducing the carbamylation motif into Cx31 created a mutant hemichannel (mCx31) that was opened by increases in PCO2. Mutation of the carbamylation motif in Cx26 and mCx31 destroyed CO2 sensitivity. Course-grained computational modelling of Cx26 demonstrated that the proposed carbamate bridge between Lys125 and Arg104 biases the hemichannel to the open state. Carbamylation of Cx26 introduces a new transduction principle for physiological sensing of CO2.