J Biol Chem. 2012 Aug 31;287(36):30305-16. doi: 10.1074/jbc.M112.394122. Epub 2012 Jul 9.
Extracellular Ca(2+) sensing in salivary ductal cells.
Bandyopadhyay, B. C., Swaim, W. D., Sarkar, A., Liu, X., Ambudkar, I. S.,
["Calcium Signaling Laboratory, Research Service, Veterans Affairs Medical Center, Washington, DC 20422, USA. bidhan.bandyopadhyay@va.gov"]
["Calcium Signaling Laboratory, Research Service, Veterans Affairs Medical Center, Washington, DC 20422, USA. bidhan.bandyopadhyay@va.gov"]
Ca(2+) is secreted from the salivary acinar cells as an ionic constituent of primary saliva. Ions such as Na(+) and Cl(-) get reabsorbed whereas primary saliva flows through the salivary ductal system. Although earlier studies have shown that salivary [Ca(2+)] decreases as it flows down the ductal tree into the oral cavity, ductal reabsorption of Ca(2+) remains enigmatic. Here we report a potential role for the G protein-coupled receptor, calcium-sensing receptor (CSR), in the regulation of Ca(2+) reabsorption by salivary gland ducts. Our data show that CSR is present in the apical region of ductal cells where it is co-localized with transient receptor potential canonical 3 (TRPC3). CSR is activated in isolated salivary gland ducts as well as a ductal cell line (SMIE) by altering extracellular [Ca(2+)] or by aromatic amino acid, L-phenylalanine (L-Phe, endogenous component of saliva), as well as neomycin. CSR activation leads to Ca(2+) influx that, in polarized cells grown on a filter support, is initiated in the luminal region. We show that TRPC3 contributes to Ca(2+) entry triggered by CSR activation. Further, stimulation of CSR in SMIE cells enhances the CSR-TRPC3 association as well as surface expression of TRPC3. Together our findings suggest that CSR could serve as a Ca(2+) sensor in the luminal membrane of salivary gland ducts and regulate reabsorption of [Ca(2+)] from the saliva via TRPC3, thus contributing to maintenance of salivary [Ca(2+)]. CSR could therefore be a potentially important protective mechanism against formation of salivary gland stones (sialolithiasis) and infection (sialoadenitis).
PMID: 22778254

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Screening
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Experimental screening | Non-experimental screening | Reference | ||||||||
TRP channel construct | Interactor source | |||||||||
TRP channel | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type | |||
TRPC3 |
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CaSR | Inference | Prediction | 22778254 |
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

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Validation: In vivo validation
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Assay with endogenous proteins | Assay with overexpressed proteins | Reference | ||||||||
Cell or tissue | Cell or tissue | TRP channel construct | Interactor construct | |||||||
TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
TRPC3 |
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CaSR | Co-immunoprecipitation | Mouse submandibular gland (SMG) ductal cell lysates | 22778254 | |||||
TRPC3 |
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CaSR | Co-immunofluorescence staining | Mouse submandibular gland (SMG) ductal tissue section | 22778254 |
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

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Functional consequence
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TRP channel | Interactor | Method | Post-translational modification | Subcellular trafficking | Activity | Reference | ||||||
TRPC3 |
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CaSR | Cell surface biotinylation | Increase in plasma membrane level | 22778254 |
(
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
