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

eLife

Christopher B Medina¹  Kodi S Ravichandran¹  Alex JB Kreutzberger²  Mark Yeager²  Xueyao Jin²  Volker Kiessling²  Lukas K Tamm²  Susan A Leonhardt²  Jorge E Contreras³  Pablo S Gaete³  Patrycja W Oleniacz⁴  Paula Q Barrett⁴  Adishesh K Narahari⁴  Yu-Hsin Chiu⁴  Douglas A Bayliss⁴ 

[1] Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, United States;Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, United States;Department of Pharmacology, Physiology, and Neuroscience, Rutgers New Jersey Medical School, Newark, United States;Department of Pharmacology, University of Virginia, Charlottesville, United States;

关键词: molecular biophysics;    Pannexin;    ion channels;    selectivity;   

DOI  :  10.7554/eLife.64787

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown