A Snapshot seminar hosted by the School of Physiology, Pharmacology and Neuroscience
Abstract: I will develop the idea that connexins originated as evolutionarily ancient CO2-sensitive ion channels that can act as a receptors for CO2-mediated signalling. I will describe our discovery of the CO2 sensitivity of connexin26 (Cx26) and its role in the chemosensory control of breathing. I will document our structural biology studies, demonstrating with cryoEM, the ability of CO2 to act on purified Cx26 to change channel conformation and our structural understanding of the mechanism of CO2 sensitivity. I shall then show that a range of other connexins possess the same CO2-binding motif and are also CO2 sensitive. I will concentrate on the newly discovered role of Cx32 in mediating local CO2 signalling. I shall demonstrate that CO2 production at the axon node as a result of action potential propagation is the essential link to Cx32 channel gating in the Schwann cell paranoid and show that Cx32 mutations that cause the peripheral neuropathy, X-linked Charcot Marie Tooth disease also alter the CO2 sensitivity of Cx32. I will briefly consider the permselectivity of connexin hemichannels to small neuroactive molecules (ATP, glutamate and lactate), before finishing with our investigations of the deep and unexpected evolutionary origins of the connexin gene family suggesting that CO2 sensing via connexin-like molecules originated in metazoa at least 630 MYA.
After the talk there will be refreshments in D1, which will provide an opportunity to network or catch up with colleagues. If you'd like to chat with the speaker while they are here, please get in touch with the host Lukasz at lukasz.chrobok@bristol.ac.uk