Pannexin 1 Signaling Metabolite Flux and Stoichiometry

Author: ORCID icon
Narahari, Adishesh, Pharmacology - School of Medicine, University of Virginia
Bayliss, Douglas, MD-PHAR Pharmacology, University of Virginia

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
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