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A quantized mechanism for activation of pannexin channels
Pannexin 1 (PANX1) subunits form oligomeric plasma membrane channels that mediate nucleotide release for purinergic signalling, which is involved in diverse physiological processes such as apoptosis, inflammation, blood pressure regulation, and cancer progression and metastasis. Here we explore the...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290276/ https://www.ncbi.nlm.nih.gov/pubmed/28134257 http://dx.doi.org/10.1038/ncomms14324 |
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author | Chiu, Yu-Hsin Jin, Xueyao Medina, Christopher B. Leonhardt, Susan A. Kiessling, Volker Bennett, Brad C. Shu, Shaofang Tamm, Lukas K. Yeager, Mark Ravichandran, Kodi S. Bayliss, Douglas A. |
author_facet | Chiu, Yu-Hsin Jin, Xueyao Medina, Christopher B. Leonhardt, Susan A. Kiessling, Volker Bennett, Brad C. Shu, Shaofang Tamm, Lukas K. Yeager, Mark Ravichandran, Kodi S. Bayliss, Douglas A. |
author_sort | Chiu, Yu-Hsin |
collection | PubMed |
description | Pannexin 1 (PANX1) subunits form oligomeric plasma membrane channels that mediate nucleotide release for purinergic signalling, which is involved in diverse physiological processes such as apoptosis, inflammation, blood pressure regulation, and cancer progression and metastasis. Here we explore the mechanistic basis for PANX1 activation by using wild type and engineered concatemeric channels. We find that PANX1 activation involves sequential stepwise sojourns through multiple discrete open states, each with unique channel gating and conductance properties that reflect contributions of the individual subunits of the hexamer. Progressive PANX1 channel opening is directly linked to permeation of ions and large molecules (ATP and fluorescent dyes) and occurs during both irreversible (caspase cleavage-mediated) and reversible (α1 adrenoceptor-mediated) forms of channel activation. This unique, quantized activation process enables fine tuning of PANX1 channel activity and may be a generalized regulatory mechanism for other related multimeric channels. |
format | Online Article Text |
id | pubmed-5290276 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-52902762017-02-07 A quantized mechanism for activation of pannexin channels Chiu, Yu-Hsin Jin, Xueyao Medina, Christopher B. Leonhardt, Susan A. Kiessling, Volker Bennett, Brad C. Shu, Shaofang Tamm, Lukas K. Yeager, Mark Ravichandran, Kodi S. Bayliss, Douglas A. Nat Commun Article Pannexin 1 (PANX1) subunits form oligomeric plasma membrane channels that mediate nucleotide release for purinergic signalling, which is involved in diverse physiological processes such as apoptosis, inflammation, blood pressure regulation, and cancer progression and metastasis. Here we explore the mechanistic basis for PANX1 activation by using wild type and engineered concatemeric channels. We find that PANX1 activation involves sequential stepwise sojourns through multiple discrete open states, each with unique channel gating and conductance properties that reflect contributions of the individual subunits of the hexamer. Progressive PANX1 channel opening is directly linked to permeation of ions and large molecules (ATP and fluorescent dyes) and occurs during both irreversible (caspase cleavage-mediated) and reversible (α1 adrenoceptor-mediated) forms of channel activation. This unique, quantized activation process enables fine tuning of PANX1 channel activity and may be a generalized regulatory mechanism for other related multimeric channels. Nature Publishing Group 2017-01-30 /pmc/articles/PMC5290276/ /pubmed/28134257 http://dx.doi.org/10.1038/ncomms14324 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Chiu, Yu-Hsin Jin, Xueyao Medina, Christopher B. Leonhardt, Susan A. Kiessling, Volker Bennett, Brad C. Shu, Shaofang Tamm, Lukas K. Yeager, Mark Ravichandran, Kodi S. Bayliss, Douglas A. A quantized mechanism for activation of pannexin channels |
title | A quantized mechanism for activation of pannexin channels |
title_full | A quantized mechanism for activation of pannexin channels |
title_fullStr | A quantized mechanism for activation of pannexin channels |
title_full_unstemmed | A quantized mechanism for activation of pannexin channels |
title_short | A quantized mechanism for activation of pannexin channels |
title_sort | quantized mechanism for activation of pannexin channels |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290276/ https://www.ncbi.nlm.nih.gov/pubmed/28134257 http://dx.doi.org/10.1038/ncomms14324 |
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