Pannexin 1 Signaling Metabolite Flux and Stoichiometry 294 views

Pannexin 1 (Panx1) channels are ion channels expressed in a wide range of tissues in vertebrate animals. Panx1 is predicted to be responsible for the release of ATP and other large signaling metabolites from cells. Panx1 has numerous activation mechanisms including via Gq-GPCRs and via C-terminal tail cleavage. The channel is important in this regard for various cell signaling pathways in numerous (patho)physiological processes. Despite works by previous groups, there are still numerous questions regarding important Panx1 channel properties: 1) Do caspase-activated Panx1 channels form a conduit that allows for the direct permeation of large signaling molecules and dye? 2) What is the functional oligomeric state of Panx1 channels? First, I utilize a biochemically-reduced proteoliposome system wherein I reconstitute Panx1 and show that caspase-activation of the channel forms a pore capable of fluxing dye, ATP, and other large signaling metabolites. Second, I use concatenated Panx1 constructs to demonstrate that Panx1 may be functional as both a hexamer and a heptamer. These works further our understanding of the Pannexin 1 channel and lead to new questions for which I have provided suggestions regarding future studies.

PHD (Doctor of Philosophy)

Pannexin 1; Ion Channels; Metabolites

English

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2021-04-13