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Role of an Aromatic–Aromatic Interaction in the Assembly and Trafficking of the Zebrafish Panx1a Membrane Channel

Pannexin 1 (Panx1) is a ubiquitously expressed hexameric integral membrane protein known to function as an adenosine triphosphate (ATP) release channel. Panx1 proteins exist in unglycosylated core form (Gly0). They undergo critical post-translational modifications forming the high mannose glycosylat...

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Autores principales: Timonina, Ksenia, Kotova, Anna, Zoidl, Georg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072349/
https://www.ncbi.nlm.nih.gov/pubmed/32053881
http://dx.doi.org/10.3390/biom10020272
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author Timonina, Ksenia
Kotova, Anna
Zoidl, Georg
author_facet Timonina, Ksenia
Kotova, Anna
Zoidl, Georg
author_sort Timonina, Ksenia
collection PubMed
description Pannexin 1 (Panx1) is a ubiquitously expressed hexameric integral membrane protein known to function as an adenosine triphosphate (ATP) release channel. Panx1 proteins exist in unglycosylated core form (Gly0). They undergo critical post-translational modifications forming the high mannose glycosylation state (Gly1) in the endoplasmic reticulum (ER) and the complex glycosylation state (Gly2) in the Golgi apparatus. The regulation of transition from the ER to the cell membrane is not fully understood. Using site-specific mutagenesis, dye uptake assays, and interaction testing, we identified two conserved aromatic residues, Trp123 and Tyr205, in the transmembrane domains 2 and 3 of the zebrafish panx1a protein. Results suggest that both residues primarily govern the assembly of panx1a subunits into channels, with mutant proteins failing to interact. The results provide insight into a mechanism enabling regulation of Panx1 oligomerization, glycosylation, and trafficking.
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spelling pubmed-70723492020-03-19 Role of an Aromatic–Aromatic Interaction in the Assembly and Trafficking of the Zebrafish Panx1a Membrane Channel Timonina, Ksenia Kotova, Anna Zoidl, Georg Biomolecules Article Pannexin 1 (Panx1) is a ubiquitously expressed hexameric integral membrane protein known to function as an adenosine triphosphate (ATP) release channel. Panx1 proteins exist in unglycosylated core form (Gly0). They undergo critical post-translational modifications forming the high mannose glycosylation state (Gly1) in the endoplasmic reticulum (ER) and the complex glycosylation state (Gly2) in the Golgi apparatus. The regulation of transition from the ER to the cell membrane is not fully understood. Using site-specific mutagenesis, dye uptake assays, and interaction testing, we identified two conserved aromatic residues, Trp123 and Tyr205, in the transmembrane domains 2 and 3 of the zebrafish panx1a protein. Results suggest that both residues primarily govern the assembly of panx1a subunits into channels, with mutant proteins failing to interact. The results provide insight into a mechanism enabling regulation of Panx1 oligomerization, glycosylation, and trafficking. MDPI 2020-02-11 /pmc/articles/PMC7072349/ /pubmed/32053881 http://dx.doi.org/10.3390/biom10020272 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Timonina, Ksenia
Kotova, Anna
Zoidl, Georg
Role of an Aromatic–Aromatic Interaction in the Assembly and Trafficking of the Zebrafish Panx1a Membrane Channel
title Role of an Aromatic–Aromatic Interaction in the Assembly and Trafficking of the Zebrafish Panx1a Membrane Channel
title_full Role of an Aromatic–Aromatic Interaction in the Assembly and Trafficking of the Zebrafish Panx1a Membrane Channel
title_fullStr Role of an Aromatic–Aromatic Interaction in the Assembly and Trafficking of the Zebrafish Panx1a Membrane Channel
title_full_unstemmed Role of an Aromatic–Aromatic Interaction in the Assembly and Trafficking of the Zebrafish Panx1a Membrane Channel
title_short Role of an Aromatic–Aromatic Interaction in the Assembly and Trafficking of the Zebrafish Panx1a Membrane Channel
title_sort role of an aromatic–aromatic interaction in the assembly and trafficking of the zebrafish panx1a membrane channel
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072349/
https://www.ncbi.nlm.nih.gov/pubmed/32053881
http://dx.doi.org/10.3390/biom10020272
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