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Pannexin-1 Activation by Phosphorylation Is Crucial for Platelet Aggregation and Thrombus Formation
Pannexin-1 (PANX1) is a transmembrane protein that forms ion channels as hexamers on the plasma membrane. Electrophysiological studies prove that PANX1 has a high conductance for adenosine triphosphate (ATP), which plays an important role as a signal molecule in platelet activation. Recently, it was...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100471/ https://www.ncbi.nlm.nih.gov/pubmed/35563450 http://dx.doi.org/10.3390/ijms23095059 |
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author | Metz, Lisa Maria Elvers, Margitta |
author_facet | Metz, Lisa Maria Elvers, Margitta |
author_sort | Metz, Lisa Maria |
collection | PubMed |
description | Pannexin-1 (PANX1) is a transmembrane protein that forms ion channels as hexamers on the plasma membrane. Electrophysiological studies prove that PANX1 has a high conductance for adenosine triphosphate (ATP), which plays an important role as a signal molecule in platelet activation. Recently, it was shown that PANX1 channels modulate platelet functions. To date, it remains unclear how PANX1 channels are activated and which signaling mechanisms are responsible for impaired hemostasis and thrombosis. Analysis of PANX1 phosphorylation at Tyr(198) and Tyr(308), and the impact on platelet activation and thrombus formation using genetically modified platelets or pharmacological inhibitors. Platelet activation via immunoreceptor tyrosine-based activation motif (ITAM) coupled, G Protein-Coupled Receptors (GPCR) and thromboxane receptor (TP)-mediated signaling pathways led to increased PANX1 phosphorylation at Tyr(198) and Tyr(308). We identified the Src-GPVI signaling axes as the main pathway inducing PANX1 activation, while PKC and Akt play a minor role. PANX1 channels function as ATP release channels in platelets to support arterial thrombus formation. PANX1 activation is regulated by phosphorylation at Tyr(198) and Tyr(308) following platelet activation. These results suggest an important role of PANX1 in hemostasis and thrombosis by releasing extracellular ATP to support thrombus formation. |
format | Online Article Text |
id | pubmed-9100471 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91004712022-05-14 Pannexin-1 Activation by Phosphorylation Is Crucial for Platelet Aggregation and Thrombus Formation Metz, Lisa Maria Elvers, Margitta Int J Mol Sci Article Pannexin-1 (PANX1) is a transmembrane protein that forms ion channels as hexamers on the plasma membrane. Electrophysiological studies prove that PANX1 has a high conductance for adenosine triphosphate (ATP), which plays an important role as a signal molecule in platelet activation. Recently, it was shown that PANX1 channels modulate platelet functions. To date, it remains unclear how PANX1 channels are activated and which signaling mechanisms are responsible for impaired hemostasis and thrombosis. Analysis of PANX1 phosphorylation at Tyr(198) and Tyr(308), and the impact on platelet activation and thrombus formation using genetically modified platelets or pharmacological inhibitors. Platelet activation via immunoreceptor tyrosine-based activation motif (ITAM) coupled, G Protein-Coupled Receptors (GPCR) and thromboxane receptor (TP)-mediated signaling pathways led to increased PANX1 phosphorylation at Tyr(198) and Tyr(308). We identified the Src-GPVI signaling axes as the main pathway inducing PANX1 activation, while PKC and Akt play a minor role. PANX1 channels function as ATP release channels in platelets to support arterial thrombus formation. PANX1 activation is regulated by phosphorylation at Tyr(198) and Tyr(308) following platelet activation. These results suggest an important role of PANX1 in hemostasis and thrombosis by releasing extracellular ATP to support thrombus formation. MDPI 2022-05-02 /pmc/articles/PMC9100471/ /pubmed/35563450 http://dx.doi.org/10.3390/ijms23095059 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Metz, Lisa Maria Elvers, Margitta Pannexin-1 Activation by Phosphorylation Is Crucial for Platelet Aggregation and Thrombus Formation |
title | Pannexin-1 Activation by Phosphorylation Is Crucial for Platelet Aggregation and Thrombus Formation |
title_full | Pannexin-1 Activation by Phosphorylation Is Crucial for Platelet Aggregation and Thrombus Formation |
title_fullStr | Pannexin-1 Activation by Phosphorylation Is Crucial for Platelet Aggregation and Thrombus Formation |
title_full_unstemmed | Pannexin-1 Activation by Phosphorylation Is Crucial for Platelet Aggregation and Thrombus Formation |
title_short | Pannexin-1 Activation by Phosphorylation Is Crucial for Platelet Aggregation and Thrombus Formation |
title_sort | pannexin-1 activation by phosphorylation is crucial for platelet aggregation and thrombus formation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100471/ https://www.ncbi.nlm.nih.gov/pubmed/35563450 http://dx.doi.org/10.3390/ijms23095059 |
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