AI Article Synopsis
- Pannexin 1 (PANX1) channels are essential for purinergic signaling and play a role in various physiological functions like inflammation, apoptosis, and cancer progression.
- The activation of PANX1 involves multiple unique open states that relate to the gating and conductance properties influenced by the individual subunits of the channel.
- This activation process allows for precise regulation of PANX1 channel activity, suggesting it may be a common mechanism for other similar multimeric channels.
Article Abstract
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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5290276 | PMC |
| http://dx.doi.org/10.1038/ncomms14324 | DOI Listing |
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