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Published on: May 17, 2019
Ano6 disruption impairs acinar cell regulatory volume decrease and protein secretion in murine submandibular salivary
Takashi Munemasa1,2, Xin Gao1, James E Melvin1
1Secretory Mechanisms and Dysfunctions Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland.
Abstract:
The widely expressed Anoctamin 6 (Ano6) supports different Ca2+ -dependent functions, but little is known about its role in salivary glands. Mouse submandibular gland (SMG) acinar cells exhibited a robust regulatory volume decrease (RVD) following cell swelling that was reduced approximately 70% in Ano6-/- mice. Ca2+ -free conditions nearly eliminated the RVD response suggesting that Ano6 is an obligatory component of the cell volume-activated, Ca2+ -dependent RVD pathway in salivary gland acinar cells. Ex vivo agonist-stimulated secretion of water and ions was unaffected by Ano6 disruption under both isotonic and hypotonic conditions suggesting that Ano6 does not play a major role in fluid and electrolyte secretion. In contrast, the total amount of β-adrenergic-dependent protein secretion by the SMG was significantly reduced in Ano6-/- mice. Closer inspection of these latter results revealed that protein secretion was affected only in the female SMG by Ano6 disruption. These results indicate that Ano6 modulates the RVD response and protein secretion by salivary gland acinar cells.
Insights
Anoctamin 6 (Ano6) is crucial for salivary gland cell volume regulation and protein secretion, particularly in females. Its absence significantly impairs regulatory volume decrease (RVD) and affects β-adrenergic-dependent protein release.
Area of Science:
- Cell biology
- Physiology
- Ion channel function
Background:
- Anoctamin 6 (Ano6) is a widely expressed calcium-dependent protein.
- Its specific functions in salivary glands remain largely uncharacterized.
- Ano6 is implicated in various cellular processes.
Purpose of the Study:
- To investigate the role of Ano6 in salivary gland acinar cell function.
- To determine Ano6's involvement in regulatory volume decrease (RVD) and secretion.
- To explore potential sex-specific effects of Ano6 in salivary glands.
Main Methods:
- Utilized Ano6 knockout (Ano6-/-) mouse models.
- Assessed regulatory volume decrease (RVD) in submandibular gland (SMG) acinar cells.
- Measured ex vivo agonist-stimulated secretion of water, ions, and proteins.
Main Results:
- Ano6 deficiency significantly reduced RVD by approximately 70% in SMG acinar cells.
- Ano6 is essential for the calcium-dependent RVD pathway in salivary glands.
- Ano6 disruption did not affect water and ion secretion but reduced female-specific β-adrenergic-dependent protein secretion.
Conclusions:
- Ano6 plays a significant role in regulating salivary gland acinar cell volume.
- Ano6 modulates β-adrenergic-stimulated protein secretion, with a notable effect in female SMGs.
- Ano6's function extends to both cell volume homeostasis and specific secretory pathways in salivary glands.
