TY - JOUR TI - ATP and large signaling metabolites flux through caspase-activated Pannexin 1 channels AU - Narahari, Adishesh K AU - Kreutzberger, Alex JB AU - Gaete, Pablo S AU - Chiu, Yu-Hsin AU - Leonhardt, Susan A AU - Medina, Christopher B AU - Jin, Xueyao AU - Oleniacz, Patrycja W AU - Kiessling, Volker AU - Barrett, Paula Q AU - Ravichandran, Kodi S AU - Yeager, Mark AU - Contreras, Jorge E AU - Tamm, Lukas K AU - Bayliss, Douglas A A2 - Chanda, Baron A2 - Swartz, Kenton J A2 - Chanda, Baron VL - 10 PY - 2021 DA - 2021/01/07 SP - e64787 C1 - eLife 2021;10:e64787 DO - 10.7554/eLife.64787 UR - https://doi.org/10.7554/eLife.64787 AB - 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. KW - molecular biophysics KW - Pannexin KW - ion channels KW - selectivity JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -