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CO2 directly modulates connexin 26 by formation of carbamate bridges between subunits
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Meigh, Louise, Greenhalgh, Sophie A., Rodgers, Thomas L., Cann, Martin J., Roper, David I. and Dale, Nicholas (2013) CO2 directly modulates connexin 26 by formation of carbamate bridges between subunits. eLife, Volume 2 . Article number e01213. doi:10.7554/eLife.01213
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Official URL: http://dx.doi.org/10.7554/eLife.01213
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.
| Item Type: | Journal Article | ||||
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| Subjects: | Q Science > QH Natural history > QH301 Biology | ||||
| Divisions: | Faculty of Science > Life Sciences (2010- ) | ||||
| Library of Congress Subject Headings (LCSH): | Carbon dioxide , Connexins, Cell metabolism, Cell respiration | ||||
| Journal or Publication Title: | eLife | ||||
| Publisher: | eLife Sciences Publications Ltd. | ||||
| ISSN: | 2050-084X | ||||
| Official Date: | 2013 | ||||
| Dates: |
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| Volume: | Volume 2 | ||||
| Page Range: | Article number e01213 | ||||
| DOI: | 10.7554/eLife.01213 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Open Access | ||||
| Funder: | Medical Research Council (Great Britain) (MRC), Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Engineering and Physical Sciences Research Council (EPSRC) | ||||
| Grant number: | G1001259 (MRC) ; EP/H051759/1 (EPSRC) |
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