Structural determinants of CO2-sensitivity in the β connexin family suggested by evolutionary analysis
| Autor: | Elizabeth de Wolf, Jonathan Cook, Valentin-Mihai Dospinescu, Maria Assunta Biscotti, Fokion Spanos, Marco Gerdol, Nicholas Dale, Sarbjit Nijjar |
|---|---|
| Přispěvatelé: | Dospinescu, Valentin-Mihai, Nijjar, Sarbjit, Spanos, Fokion, Cook, Jonathan, de Wolf, Elizabeth, Biscotti, Maria Assunta, Gerdol, Marco, Dale, Nicholas |
| Rok vydání: | 2019 |
| Předmět: |
connexin
Medicine (miscellaneous) Connexin amphibia General Biochemistry Genetics and Molecular Biology Connexon 03 medical and health sciences 0302 clinical medicine Molecular evolution otorhinolaryngologic diseases lungfish lcsh:QH301-705.5 030304 developmental biology CO2 sensing Lungfish 0303 health sciences biology Chemistry QH Co2 sensitivity biology.organism_classification QP Cell biology lcsh:Biology (General) General Agricultural and Biological Sciences 030217 neurology & neurosurgery |
| Zdroj: | Communications Biology, Vol 2, Iss 1, Pp 1-14 (2019) |
| ISSN: | 2399-3642 |
| DOI: | 10.1038/s42003-019-0576-2 |
| Popis: | A subclade of connexins comprising Cx26, Cx30, and Cx32 are directly sensitive to CO2. CO2 binds to a carbamylation motif present in these connexins and causes their hemichannels to open. Cx26 may contribute to CO2-dependent regulation of breathing in mammals. Here, we show that the carbamylation motif occurs in a wide range of non-mammalian vertebrates and was likely present in the ancestor of all gnathostomes. While the carbamylation motif is essential for connexin CO2-sensitivity, it is not sufficient. In Cx26 of amphibia and lungfish, an extended C-terminal tail prevents CO2-evoked hemichannel opening despite the presence of the motif. Although Cx32 has a long C-terminal tail, Cx32 hemichannels open to CO2 because the tail is conformationally restricted by the presence of proline residues. The loss of the C-terminal tail of Cx26 in amniotes was an evolutionary innovation that created a connexin hemichannel with CO2-sensing properties suitable for the regulation of breathing. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|