Syntaxin-3 Mediates Baseline Mucin Secretion in Club Cells

Abstract Purpose Nasal irrigation is an effective method for alleviating several nasal symptoms and regular seawater-based nasal irrigation is useful for maintaining nasal hygiene which is essential for appropriate functioning of the nose and for preventing airborne particles including some pollutants, pathogens, and allergens from moving further in the respiratory system. However, safety studies on seawater-based nasal irrigation are scarce. In this study, the safety and efficacy of a diluted isotonic seawater solution (Stérimar Nasal Hygiene, SNH) in maintaining nasal homeostasis were evaluated in vitro. Methods Safety was assessed by measuring tissue integrity via transepithelial electrical resistance (TEER). Efficacy was measured by mucociliary clearance (MCC), mucin secretion, and tissue re-epithelization (wound repair) assays. All assays were performed using a 3D reconstituted human nasal epithelium model. Results In SNH-treated tissues, TEER values were statistically significantly lower than the untreated tissues; however, the values were above the tissue integrity limit. SNH treatment significantly increased MCC (88 vs. 36 µm/s, p < 0.001) and mucin secretion (1717 vs. 1280 µg/ml, p < 0.001) as compared to untreated cultures. Faster wound closure profile was noted upon pre-SNH treatment as compared to classical isotonic saline solution pre-treatment (90.5 vs. 50.7% wound closure 22 h after wound generation). Conclusion SNH did not compromise the integrity of the nasal epithelium in vitro. Furthermore, SNH was effective for removal of foreign particles through MCC increase and for enhancing wound repair on nasal mucosa.

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Syntaxin 3 interacts with serotonin transporter and regulates its function

Journal of Pharmacological Sciences ◽

10.1016/j.jphs.2021.01.007 ◽

2021 ◽

Vol 145 (4) ◽

pp. 297-307

Author(s):

Serika Motoike ◽

Kei Taguchi ◽

Kana Harada ◽

Masaya Asano ◽

Izumi Hide ◽

...

Keyword(s):

Serotonin Transporter ◽

Syntaxin 3

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Vasoactive intestinal peptide stimulates mucus secretion, but nitric oxide has no effect on mucus secretion in the ferret trachea

Journal of Applied Physiology ◽

10.1152/japplphysiol.01264.2005 ◽

2006 ◽

Vol 101 (2) ◽

pp. 486-491 ◽

Cited By ~ 8

Author(s):

Jung-Soo Kim ◽

Kosuke Okamoto ◽

Shinobu Arima ◽

Bruce K. Rubin

Keyword(s):

Nitric Oxide ◽

Receptor Antagonist ◽

Vasoactive Intestinal Peptide ◽

Mucus Secretion ◽

Cell Secretion ◽

Mucin Secretion ◽

No Donor ◽

Peptide Analog ◽

Dose Dependent ◽

Vip Receptor

Vasoactive intestinal peptide (VIP) and nitric oxide (NO) are neurotransmitters involved in the regulation of bronchial and pulmonary vascular tone. Published studies of the effects of VIP on airway mucus secretion have yielded conflicting results. The purpose of this study was to determine the effect of VIP on mucus secretion in the ferret trachea and if this effect was influenced by NO. We used a sandwich enzyme-linked lectin assay to measure mucin secretion and a turbidimetric assay to measure lysozyme (serous cell) secretion from ferret tracheal segments. VIP (10−7 M) increased mucin secretion over 2 h. VIP (10−9 to 10−5 M) stimulated mucin secretion in a dose-dependent fashion. VIP-induced mucin secretion was partially blocked by a VIP receptor antagonist (a chimeric VIP-pituitary adenylate cyclase-activating peptide analog, VIP receptor antagonist) at a 10-fold excess concentration. At all concentrations tested, neither NG-nitro-l-arginine methyl ester, an inhibitor of NO synthase, nor S-nitroso- N-acetyl-penicillamine, an NO donor, had any significant effect on constitutive or VIP-induced mucus secretion. We conclude that VIP-stimulated mucin and lysozyme secretion was both time dependent and dose dependent and that NO neither stimulates nor inhibits mucus secretion in the ferret trachea.

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Carbenoxolone and triterpenoids inhibited mucin secretion from airway epithelial cells

Phytotherapy Research ◽

10.1002/ptr.2102 ◽

2007 ◽

Vol 21 (5) ◽

pp. 462-465 ◽

Cited By ~ 22

Author(s):

Ho Jin Heo ◽

Cheolsu Kim ◽

Hyun Jae Lee ◽

Young Sik Kim ◽

Sam Sik Kang ◽

...

Keyword(s):

Epithelial Cells ◽

Airway Epithelial Cells ◽

Airway Epithelial ◽

Mucin Secretion

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Barrier role of actin filaments in regulated mucin secretion from airway goblet cells

AJP Cell Physiology ◽

10.1152/ajpcell.00397.2004 ◽

2005 ◽

Vol 288 (1) ◽

pp. C46-C56 ◽

Cited By ~ 50

Author(s):

Camille Ehre ◽

Andrea H. Rossi ◽

Lubna H. Abdullah ◽

Kathleen De Pestel ◽

Sandra Hill ◽

...

Keyword(s):

Plasma Membrane ◽

Actin Filaments ◽

Fluorescent Protein ◽

Secretory Granules ◽

Yellow Fluorescent Protein ◽

Goblet Cells ◽

Actin Binding ◽

Secretory Cells ◽

Cortical Actin ◽

Mucin Secretion

Airway goblet cells secrete mucin onto mucosal surfaces under the regulation of an apical, phospholipase C/Gq-coupled P2Y2receptor. We tested whether cortical actin filaments negatively regulate exocytosis in goblet cells by forming a barrier between secretory granules and plasma membrane docking sites as postulated for other secretory cells. Immunostaining of human lung tissues and SPOC1 cells (an epithelial, mucin-secreting cell line) revealed an apical distribution of β- and γ-actin in ciliated and goblet cells. In goblet cells, actin appeared as a prominent subplasmalemmal sheet lying between granules and the apical membrane, and it disappeared from SPOC1 cells activated by purinergic agonist. Disruption of actin filaments with latrunculin A stimulated SPOC1 cell mucin secretion under basal and agonist-activated conditions, whereas stabilization with jasplakinolide or overexpression of β- or γ-actin conjugated to yellow fluorescent protein (YFP) inhibited secretion. Myristoylated alanine-rich C kinase substrate, a PKC-activated actin-plasma membrane tethering protein, was phosphorylated after agonist stimulation, suggesting a translocation to the cytosol. Scinderin (or adseverin), a Ca2+-activated actin filament severing and capping protein was cloned from human airway and SPOC1 cells, and synthetic peptides corresponding to its actin-binding domains inhibited mucin secretion. We conclude that actin filaments negatively regulate mucin secretion basally in airway goblet cells and are dynamically remodeled in agonist-stimulated cells to promote exocytosis.

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A Novel Tetanus Neurotoxin-insensitive Vesicle-associated Membrane Protein in SNARE Complexes of the Apical Plasma Membrane of Epithelial Cells

Molecular Biology of the Cell ◽

10.1091/mbc.9.6.1437 ◽

1998 ◽

Vol 9 (6) ◽

pp. 1437-1448 ◽

Cited By ~ 210

Author(s):

Thierry Galli ◽

Ahmed Zahraoui ◽

Vadakkanchery V. Vaidyanathan ◽

Graça Raposo ◽

Jian Min Tian ◽

...

Keyword(s):

Plasma Membrane ◽

Epithelial Cells ◽

Membrane Protein ◽

Apical Plasma Membrane ◽

Domain Specific ◽

Tetanus Neurotoxin ◽

Synaptic Vesicle Exocytosis ◽

Clostridial Neurotoxins ◽

Vesicle Exocytosis ◽

Syntaxin 3

The importance of soluble N-ethyl maleimide (NEM)-sensitive fusion protein (NSF) attachment protein (SNAP) receptors (SNAREs) in synaptic vesicle exocytosis is well established because it has been demonstrated that clostridial neurotoxins (NTs) proteolyze the vesicle SNAREs (v-SNAREs) vesicle-associated membrane protein (VAMP)/brevins and their partners, the target SNAREs (t-SNAREs) syntaxin 1 and SNAP25. Yet, several exocytotic events, including apical exocytosis in epithelial cells, are insensitive to numerous clostridial NTs, suggesting the presence of SNARE-independent mechanisms of exocytosis. In this study we found that syntaxin 3, SNAP23, and a newly identified VAMP/brevin, tetanus neurotoxin (TeNT)-insensitive VAMP (TI-VAMP), are insensitive to clostridial NTs. In epithelial cells, TI-VAMP–containing vesicles were concentrated in the apical domain, and the protein was detected at the apical plasma membrane by immunogold labeling on ultrathin cryosections. Syntaxin 3 and SNAP23 were codistributed at the apical plasma membrane where they formed NEM-dependent SNARE complexes with TI-VAMP and cellubrevin. We suggest that TI-VAMP, SNAP23, and syntaxin 3 can participate in exocytotic processes at the apical plasma membrane of epithelial cells and, more generally, domain-specific exocytosis in clostridial NT-resistant pathways.

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