Polycystin-2 In Mouse Lacrimal Gland Acinar Cells

Abstract

Purpose: : Lacrimal glands regulate the production and secretion of tear fluid. Tear secretion from the acinar cells of the lacrimal gland is regulated by both cholinergic and adrenergic stimuli, which both result in changes in the cytosolic Ca²⁺ concentration. Dysfunction of lacrimal gland acinar cells resulting in aberrant Ca²⁺ homeostasis is associated with dry-eye disease and Sjögren’s syndrome, and approaches targeting intracellular Ca²⁺ signaling may be of therapeutic benefit for these diseases. We have previously described the detailed intracellular distribution of inositol 1,4,5-trisphosphate receptors and ryanodine receptors in lacrimal acinar cells (Medina-Ortiz et al., Open Ophthalmol J. 2007; 1: 8-16). However, little is known regarding the expression, distribution and localization of another major intracellular Ca²⁺ release channel, polycystin-2. The polycystin group of proteins contains non-selective cation channels related to the transient receptor potential channel superfamily (Koulen et al., Nat. Cell Biol. 2002; 4: 191-7). The present study’s goal was to identify the functional localization and activity of polycystin-2 in lacrimal acinar cells.

Methods: : Functional localization and biophysical properties of polycystin-2 from adult lacrimal gland tissue of Swiss-Webster mice (The Jackson Laboratory, Bar Harbor, ME) were determined using immunoblotting, immunohistochemistry, laser scanning and electron microscopy and single channel electrophysiology.

Results: : We identified strong cytosolic polycystin-2 immunoreactivity in lacrimal acinar cells. Subcellular analysis of immunogold labeling revealed strongest expression on the membranes of the endoplasmic reticulum, Golgi and nucleus, indicating functional localization as an intracellular Ca²⁺ release channel. Biophysical properties of lacrimal gland polycystin-2 channels were similar to those described for other tissues.

Conclusions: : Expression in lacrimal acinar cells suggests a functional role of polycystins in the regulation of lacrimal fluid secretion through Ca²⁺ induced Ca²⁺ release under physiological and disease conditions, and provides the basis for future studies focusing on physiology and pharmacology of dry-eye disease and Sjögren’s syndrome.

Keywords: lacrimal gland • calcium • ion channels