Role of Orai1 and store-operated calcium entry in mouse lacrimal gland signalling and function

Xing, Juan, Petranka, John G., Davis, Felicity M., Desai, Pooja N., Putney, James W. and Bird, Gary S. (2014) Role of Orai1 and store-operated calcium entry in mouse lacrimal gland signalling and function. The Journal of Physiology, 592 5: 927-939. doi:10.1113/jphysiol.2013.267740


Author Xing, Juan
Petranka, John G.
Davis, Felicity M.
Desai, Pooja N.
Putney, James W.
Bird, Gary S.
Title Role of Orai1 and store-operated calcium entry in mouse lacrimal gland signalling and function
Journal name The Journal of Physiology   Check publisher's open access policy
ISSN 0022-3751
1469-7793
Publication date 2014-03-01
Year available 2014
Sub-type Article (original research)
DOI 10.1113/jphysiol.2013.267740
Volume 592
Issue 5
Start page 927
End page 939
Total pages 13
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
Lacrimal glands function to produce an aqueous layer, or tear film, that helps to nourish and protect the ocular surface. Lacrimal glands secrete proteins, electrolytes and water, and loss of gland function can result in tear film disorders such as dry eye syndrome, a widely encountered and debilitating disease in ageing populations. To combat these disorders, understanding the underlying molecular signalling processes that control lacrimal gland function will give insight into corrective therapeutic approaches. Previously, in single lacrimal cells isolated from lacrimal glands, we demonstrated that muscarinic receptor activation stimulates a phospholipase C-coupled signalling cascade involving the inositol trisphosphate-dependent mobilization of intracellular calcium and the subsequent activation of store-operated calcium entry (SOCE). Since intracellular calcium stores are finite and readily exhausted, the SOCE pathway is a critical process for sustaining and maintaining receptor-activated signalling. Recent studies have identified the Orai family proteins as critical components of the SOCE channel activity in a wide variety of cell types. In this study we characterize the role of Orai1 in the function of lacrimal glands using a mouse model in which the gene for the calcium entry channel protein, Orai1, has been deleted. Our data demonstrate that lacrimal acinar cells lacking Orai1 do not exhibit SOCE following activation of the muscarinic receptor. In comparison with wild-type and heterozygous littermates, Orai1 knockout mice showed a significant reduction in the stimulated tear production following injection of pilocarpine, a muscarinic receptor agonist. In addition, calcium-dependent, but not calcium-independent exocytotic secretion of peroxidase was eliminated in glands from knockout mice. These studies indicate a critical role for Orai1-mediated SOCE in lacrimal gland signalling and function.
Keyword Lacrimal gland
Store operated calcium entry
Orai1
Calcium signalling
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Pharmacy Publications
 
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Created: Sun, 23 Aug 2015, 06:33:03 EST by Miss Felicity Davis on behalf of School of Pharmacy