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TMEM16A/F support exocytosis but do not inhibit Notch-mediated goblet cell metaplasia of BCi-NS1.1 human airway epithelium

Cl(−) channels such as the Ca(2+) activated Cl(−) channel TMEM16A and the Cl(−) permeable phospholipid scramblase TMEM16F may affect the intracellular Cl(−) concentration ([Cl(−)](i)), which could act as an intracellular signal. Loss of airway expression of TMEM16A induced a massive expansion of the...

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Autores principales: Centeio, Raquel, Cabrita, Inês, Schreiber, Rainer, Kunzelmann, Karl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10206426/
https://www.ncbi.nlm.nih.gov/pubmed/37234411
http://dx.doi.org/10.3389/fphys.2023.1157704
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author Centeio, Raquel
Cabrita, Inês
Schreiber, Rainer
Kunzelmann, Karl
author_facet Centeio, Raquel
Cabrita, Inês
Schreiber, Rainer
Kunzelmann, Karl
author_sort Centeio, Raquel
collection PubMed
description Cl(−) channels such as the Ca(2+) activated Cl(−) channel TMEM16A and the Cl(−) permeable phospholipid scramblase TMEM16F may affect the intracellular Cl(−) concentration ([Cl(−)](i)), which could act as an intracellular signal. Loss of airway expression of TMEM16A induced a massive expansion of the secretory cell population like goblet and club cells, causing differentiation into a secretory airway epithelium. Knockout of the Ca(2+)-activated Cl(−) channel TMEM16A or the phospholipid scramblase TMEM16F leads to mucus accumulation in intestinal goblet cells and airway secretory cells. We show that both TMEM16A and TMEM16F support exocytosis and release of exocytic vesicles, respectively. Lack of TMEM16A/F expression therefore causes inhibition of mucus secretion and leads to goblet cell metaplasia. The human basal epithelial cell line BCi-NS1.1 forms a highly differentiated mucociliated airway epithelium when grown in PneumaCult™ media under an air liquid interface. The present data suggest that mucociliary differentiation requires activation of Notch signaling, but not the function of TMEM16A. Taken together, TMEM16A/F are important for exocytosis, mucus secretion and formation of extracellular vesicles (exosomes or ectosomes) but the present data do no not support a functional role of TMEM16A/F in Notch-mediated differentiation of BCi-NS1.1 cells towards a secretory epithelium.
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spelling pubmed-102064262023-05-25 TMEM16A/F support exocytosis but do not inhibit Notch-mediated goblet cell metaplasia of BCi-NS1.1 human airway epithelium Centeio, Raquel Cabrita, Inês Schreiber, Rainer Kunzelmann, Karl Front Physiol Physiology Cl(−) channels such as the Ca(2+) activated Cl(−) channel TMEM16A and the Cl(−) permeable phospholipid scramblase TMEM16F may affect the intracellular Cl(−) concentration ([Cl(−)](i)), which could act as an intracellular signal. Loss of airway expression of TMEM16A induced a massive expansion of the secretory cell population like goblet and club cells, causing differentiation into a secretory airway epithelium. Knockout of the Ca(2+)-activated Cl(−) channel TMEM16A or the phospholipid scramblase TMEM16F leads to mucus accumulation in intestinal goblet cells and airway secretory cells. We show that both TMEM16A and TMEM16F support exocytosis and release of exocytic vesicles, respectively. Lack of TMEM16A/F expression therefore causes inhibition of mucus secretion and leads to goblet cell metaplasia. The human basal epithelial cell line BCi-NS1.1 forms a highly differentiated mucociliated airway epithelium when grown in PneumaCult™ media under an air liquid interface. The present data suggest that mucociliary differentiation requires activation of Notch signaling, but not the function of TMEM16A. Taken together, TMEM16A/F are important for exocytosis, mucus secretion and formation of extracellular vesicles (exosomes or ectosomes) but the present data do no not support a functional role of TMEM16A/F in Notch-mediated differentiation of BCi-NS1.1 cells towards a secretory epithelium. Frontiers Media S.A. 2023-05-09 /pmc/articles/PMC10206426/ /pubmed/37234411 http://dx.doi.org/10.3389/fphys.2023.1157704 Text en Copyright © 2023 Centeio, Cabrita, Schreiber and Kunzelmann. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Centeio, Raquel
Cabrita, Inês
Schreiber, Rainer
Kunzelmann, Karl
TMEM16A/F support exocytosis but do not inhibit Notch-mediated goblet cell metaplasia of BCi-NS1.1 human airway epithelium
title TMEM16A/F support exocytosis but do not inhibit Notch-mediated goblet cell metaplasia of BCi-NS1.1 human airway epithelium
title_full TMEM16A/F support exocytosis but do not inhibit Notch-mediated goblet cell metaplasia of BCi-NS1.1 human airway epithelium
title_fullStr TMEM16A/F support exocytosis but do not inhibit Notch-mediated goblet cell metaplasia of BCi-NS1.1 human airway epithelium
title_full_unstemmed TMEM16A/F support exocytosis but do not inhibit Notch-mediated goblet cell metaplasia of BCi-NS1.1 human airway epithelium
title_short TMEM16A/F support exocytosis but do not inhibit Notch-mediated goblet cell metaplasia of BCi-NS1.1 human airway epithelium
title_sort tmem16a/f support exocytosis but do not inhibit notch-mediated goblet cell metaplasia of bci-ns1.1 human airway epithelium
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10206426/
https://www.ncbi.nlm.nih.gov/pubmed/37234411
http://dx.doi.org/10.3389/fphys.2023.1157704
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