Atp and large signaling metabolites flux through caspase-activated pannexin 1 channels

Adishesh K. Narahari, Alex J.B. Kreutzberger, Pablo S. Gaete, Yu Hsin Chiu, Susan A. Leonhardt, Christopher B. Medina, Xueyao Jin, Patrycja W. Oleniacz, Volker Kiessling, Paula Q. Barrett, Kodi S. Ravichandran, Mark Yeager, Jorge E. Contreras, Lukas K. Tamm, Douglas A. Bayliss

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere64787
Pages (from-to)1-21
Number of pages21
JournaleLife
Volume10
DOIs
StatePublished - Jan 2021

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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