Final Report Summary - LYNX3 (Molecular characterization of respiratory epithelium specific Lynx3.)
Barrier function and mucociliary clearance of the airway epithelia are innate defenses to protect the lungs from deleterious effects caused by inhaled pollutants and allergens. Cigarette smoking, induces aberrant airway epithelial structure and function, and slows cilia beating, however, the underlying mechanisms are poorly understood. In this study, we identified a novel nicotinic acetylcholine receptor modulator, Lynx3, specifically expressed in ciliated cells of the airway epithelia. Lynx3 knock-out mice exhibited attenuated responses to the aerosolized cholinergic bronchoconstrictor methacholine, but not to intravenous, methacholine treatment; suggesting that Lynx3 deficiency alters barrier function of airway epithelia. Compared to wild type mice, ciliated tracheal cells from Lynx3-/- null mice showed a small but significant increase in both basal cytosolic Ca2+ concentration and in Ca2+ mobilization in response to ATP, without changes in response to mild temperature or hypotonic conditions. Lynx3-/- ciliated cells also presented a faster increase in the ciliary beat frequency following stimulation with ATP but without changes either in basal ciliary beat frequency or in response to mild temperature and hypotonic conditions. Altogether, these findings identify a novel member of the Ly6/α neurotoxin superfamily with cholinergic activity as a modulator of Ca2+ signaling and barrier function in ciliated cells of the airways.
In addition to the scientific findings, the current IRG project has enabled the researcher to make a good start in establishing her own research group after her move from USA to Turkey. With the help of IRG support, she managed to start other research projects and publish several high impact scientific papers, in addition to mentoring several graduate students.