Document Detail


Regulated airway goblet cell mucin secretion.
MedLine Citation:
PMID:  17988208     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Major advances in understanding regulated mucin secretion from airway goblet cells have been made in the past decade in the areas of pharmacology and basic cell biology. For instance, it is now appreciated that nucleotide agonists acting locally through P2Y purinoceptors on apical membranes of surface goblet cells provide the major regulatory system for mucin secretion. Similarly, Clara cells, the primary secretory cell in the mouse airways (and human small airways), are now recognized as major mucin-secreting cells. In Clara cells, the relative lack of staining for mucosubstances reflects essentially equal baseline rates of mucin synthesis and secretion, with little to no accumulation of mucin granules in storage pools. During mucous metaplasia induced under inflammatory conditions, mucin synthesis is massively upregulated in Clara cells, and stored mucin granules come to dominate the secretory cell phenotype. More importantly, we have seen a transition in the past few years from a pharmacological focus on regulated mucin secretion to a more molecular mechanistic focus that has great promise going forward. In part, these advances are occurring through the use of well-differentiated primary human bronchial epithelial cell cultures, but recent work in mouse models perhaps has had the most important impact. Emerging data from Munc13-2- and synaptotagmin 2-deficient mouse models represent the first direct, molecular-level manipulations of proteins involved in regulated secretory cell mucin secretion. These new data indicate that Munc13-2 is responsible for regulating a baseline mucin secretory pathway in the airways and is not essential for purinergic agonist-induced mucin secretion. In contrast, synaptotagmin 2, a fast Ca2+ sensor for the SNARE complex, is essential for regulated secretion. Interestingly, these early results suggest that there are two pathways for excocytic mucin release from goblet cells.
Authors:
C William Davis; Burton F Dickey
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Annual review of physiology     Volume:  70     ISSN:  0066-4278     ISO Abbreviation:  Annu. Rev. Physiol.     Publication Date:  2008  
Date Detail:
Created Date:  2008-02-14     Completed Date:  2008-05-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370600     Medline TA:  Annu Rev Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  487-512     Citation Subset:  IM    
Affiliation:
Cystic Fibrosis/Pulmonary Research & Treatment Center, University of North Carolina, Chapel Hill, NC 27599-7248, USA. cwdavis@med.unc.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Exocytosis / physiology
Goblet Cells / cytology,  physiology*,  secretion*
Humans
Lung / cytology*,  metabolism*
Mucins / secretion*
Mucus / secretion
Grant Support
ID/Acronym/Agency:
HL063756/HL/NHLBI NIH HHS; HL072984/HL/NHLBI NIH HHS; P30CA16672/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Mucins

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