• Medientyp: E-Artikel
  • Titel: Structural determinants of CO2-sensitivity in the β connexin family suggested by evolutionary analysis
  • Beteiligte: Dospinescu, Valentin-Mihai; Nijjar, Sarbjit; Spanos, Fokion; Cook, Jonathan; de Wolf, Elizabeth; Biscotti, Maria Assunta; Gerdol, Marco; Dale, Nicholas
  • Erschienen: Springer Science and Business Media LLC, 2019
  • Erschienen in: Communications Biology
  • Sprache: Englisch
  • DOI: 10.1038/s42003-019-0576-2
  • ISSN: 2399-3642
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  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>A subclade of connexins comprising Cx26, Cx30, and Cx32 are directly sensitive to CO<jats:sub>2</jats:sub>. CO<jats:sub>2</jats:sub> binds to a carbamylation motif present in these connexins and causes their hemichannels to open. Cx26 may contribute to CO<jats:sub>2</jats:sub>-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 CO<jats:sub>2</jats:sub>-sensitivity, it is not sufficient. In Cx26 of amphibia and lungfish, an extended C-terminal tail prevents CO<jats:sub>2</jats:sub>-evoked hemichannel opening despite the presence of the motif. Although Cx32 has a long C-terminal tail, Cx32 hemichannels open to CO<jats:sub>2</jats:sub> 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 CO<jats:sub>2</jats:sub>-sensing properties suitable for the regulation of breathing.</jats:p>
  • Zugangsstatus: Freier Zugang