Skip to main content

Research Repository

Advanced Search

CO2 directly modulates connexin 26 by formation of carbamate bridges between subunits

Meigh, L.; Greenhalgh, S.A.; Rodgers, T.L.; Cann, M.J.; Roper, D.I.; Dale, N.

CO2 directly modulates connexin 26 by formation of carbamate bridges between subunits Thumbnail


Authors

L. Meigh

S.A. Greenhalgh

T.L. Rodgers

D.I. Roper

N. Dale



Abstract

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.

Journal Article Type Article
Publication Date Nov 12, 2013
Deposit Date Nov 28, 2013
Publicly Available Date Dec 1, 2014
Journal eLife
Publisher eLife Sciences Publications
Peer Reviewed Peer Reviewed
Volume 2
DOI https://doi.org/10.7554/elife.01213
Public URL https://durham-repository.worktribe.com/output/1443960

Files

Published Journal Article (3.8 Mb)
PDF

Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
Copyright © Meigh et al. This article is distributed under the
terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.






You might also like



Downloadable Citations