Cargando…
ATP and large signaling metabolites flux through caspase-activated Pannexin 1 channels
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 permea...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806264/ https://www.ncbi.nlm.nih.gov/pubmed/33410749 http://dx.doi.org/10.7554/eLife.64787 |
_version_ | 1783636491581259776 |
---|---|
author | Narahari, Adishesh K Kreutzberger, Alex JB Gaete, Pablo S Chiu, Yu-Hsin Leonhardt, Susan A Medina, Christopher B Jin, Xueyao Oleniacz, Patrycja W Kiessling, Volker Barrett, Paula Q Ravichandran, Kodi S Yeager, Mark Contreras, Jorge E Tamm, Lukas K Bayliss, Douglas A |
author_facet | Narahari, Adishesh K Kreutzberger, Alex JB Gaete, Pablo S Chiu, Yu-Hsin Leonhardt, Susan A Medina, Christopher B Jin, Xueyao Oleniacz, Patrycja W Kiessling, Volker Barrett, Paula Q Ravichandran, Kodi S Yeager, Mark Contreras, Jorge E Tamm, Lukas K Bayliss, Douglas A |
author_sort | Narahari, Adishesh K |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7806264 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-78062642021-01-15 ATP and large signaling metabolites flux through caspase-activated Pannexin 1 channels Narahari, Adishesh K Kreutzberger, Alex JB Gaete, Pablo S Chiu, Yu-Hsin Leonhardt, Susan A Medina, Christopher B Jin, Xueyao Oleniacz, Patrycja W Kiessling, Volker Barrett, Paula Q Ravichandran, Kodi S Yeager, Mark Contreras, Jorge E Tamm, Lukas K Bayliss, Douglas A eLife Structural Biology and Molecular Biophysics 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. eLife Sciences Publications, Ltd 2021-01-07 /pmc/articles/PMC7806264/ /pubmed/33410749 http://dx.doi.org/10.7554/eLife.64787 Text en © 2021, Narahari et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Structural Biology and Molecular Biophysics Narahari, Adishesh K Kreutzberger, Alex JB Gaete, Pablo S Chiu, Yu-Hsin Leonhardt, Susan A Medina, Christopher B Jin, Xueyao Oleniacz, Patrycja W Kiessling, Volker Barrett, Paula Q Ravichandran, Kodi S Yeager, Mark Contreras, Jorge E Tamm, Lukas K Bayliss, Douglas A ATP and large signaling metabolites flux through caspase-activated Pannexin 1 channels |
title | ATP and large signaling metabolites flux through caspase-activated Pannexin 1 channels |
title_full | ATP and large signaling metabolites flux through caspase-activated Pannexin 1 channels |
title_fullStr | ATP and large signaling metabolites flux through caspase-activated Pannexin 1 channels |
title_full_unstemmed | ATP and large signaling metabolites flux through caspase-activated Pannexin 1 channels |
title_short | ATP and large signaling metabolites flux through caspase-activated Pannexin 1 channels |
title_sort | atp and large signaling metabolites flux through caspase-activated pannexin 1 channels |
topic | Structural Biology and Molecular Biophysics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806264/ https://www.ncbi.nlm.nih.gov/pubmed/33410749 http://dx.doi.org/10.7554/eLife.64787 |
work_keys_str_mv | AT narahariadisheshk atpandlargesignalingmetabolitesfluxthroughcaspaseactivatedpannexin1channels AT kreutzbergeralexjb atpandlargesignalingmetabolitesfluxthroughcaspaseactivatedpannexin1channels AT gaetepablos atpandlargesignalingmetabolitesfluxthroughcaspaseactivatedpannexin1channels AT chiuyuhsin atpandlargesignalingmetabolitesfluxthroughcaspaseactivatedpannexin1channels AT leonhardtsusana atpandlargesignalingmetabolitesfluxthroughcaspaseactivatedpannexin1channels AT medinachristopherb atpandlargesignalingmetabolitesfluxthroughcaspaseactivatedpannexin1channels AT jinxueyao atpandlargesignalingmetabolitesfluxthroughcaspaseactivatedpannexin1channels AT oleniaczpatrycjaw atpandlargesignalingmetabolitesfluxthroughcaspaseactivatedpannexin1channels AT kiesslingvolker atpandlargesignalingmetabolitesfluxthroughcaspaseactivatedpannexin1channels AT barrettpaulaq atpandlargesignalingmetabolitesfluxthroughcaspaseactivatedpannexin1channels AT ravichandrankodis atpandlargesignalingmetabolitesfluxthroughcaspaseactivatedpannexin1channels AT yeagermark atpandlargesignalingmetabolitesfluxthroughcaspaseactivatedpannexin1channels AT contrerasjorgee atpandlargesignalingmetabolitesfluxthroughcaspaseactivatedpannexin1channels AT tammlukask atpandlargesignalingmetabolitesfluxthroughcaspaseactivatedpannexin1channels AT baylissdouglasa atpandlargesignalingmetabolitesfluxthroughcaspaseactivatedpannexin1channels |