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

Frontiers in Physiology

Physiology

Inês Cabrita¹  Rainer Schreiber²  Raquel Centeio²  Karl Kunzelmann² 

[1] Department II of Internal Medicine and Center for Molecular Medicine Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany;Physiological Institute, University of Regensburg, Regensburg, Germany;

关键词: TMEM16F;    exocytosis;    goblet cell metaplasia;    Notch signaling;    TMEM16A;   

DOI  :  10.3389/fphys.2023.1157704

 received in 2023-02-07, accepted in 2023-04-26,  发布年份 2023

来源: Frontiers

【 摘 要 】

Cl− channels such as the Ca2+ 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 Ca2+-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.

【 授权许可】

Unknown   
Copyright © 2023 Centeio, Cabrita, Schreiber and Kunzelmann.