ATP and large signaling metabolites flux through caspase-activated Pannexin 1 channels.

Autor:	Narahari AK; Department of Pharmacology, University of Virginia, Charlottesville, United States., Kreutzberger AJ; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States., Gaete PS; Department of Pharmacology, Physiology, and Neuroscience, Rutgers New Jersey Medical School, Newark, United States., Chiu YH; Department of Pharmacology, University of Virginia, Charlottesville, United States., Leonhardt SA; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States., Medina CB; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, United States., Jin X; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States., Oleniacz PW; Department of Pharmacology, University of Virginia, Charlottesville, United States., Kiessling V; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States., Barrett PQ; Department of Pharmacology, University of Virginia, Charlottesville, United States., Ravichandran KS; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, United States., Yeager M; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States., Contreras JE; Department of Pharmacology, Physiology, and Neuroscience, Rutgers New Jersey Medical School, Newark, United States., Tamm LK; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States., Bayliss DA; Department of Pharmacology, University of Virginia, Charlottesville, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2021 Jan 07; Vol. 10. Date of Electronic Publication: 2021 Jan 07.
DOI:	10.7554/eLife.64787
Abstrakt:	Pannexin 1 (Panx1) is a membrane channel implicated in numerous physiological and pathophysiological processes via its ability to support release of ATP and other cellular metabolites for local intercellular signaling. However, to date, there has been no direct demonstration of large molecule permeation via the Panx1 channel itself, and thus the permselectivity of Panx1 for different molecules remains unknown. To address this, we expressed, purified, and reconstituted Panx1 into proteoliposomes and demonstrated that channel activation by caspase cleavage yields a dye-permeable pore that favors flux of anionic, large-molecule permeants (up to ~1 kDa). Large cationic molecules can also permeate the channel, albeit at a much lower rate. We further show that Panx1 channels provide a molecular pathway for flux of ATP and other anionic (glutamate) and cationic signaling metabolites (spermidine). These results verify large molecule permeation directly through caspase-activated Panx1 channels that can support their many physiological roles. Competing Interests: AN, AK, PG, YC, SL, CM, XJ, PO, VK, PB, KR, MY, JC, LT, DB No competing interests declared (© 2021, Narahari et al.)
Databáze:	MEDLINE
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