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Type II epithelial cells synthesize pulmonary surfactant, a lipid-rich mixture that is stored in highly specialized secretory granules called lamellar bodies. Surfactant is secreted into the alveolar airspaces where it plays a critical role in stabilizing the gas exchange surface:
Surfactant secretion must therefore be balanced by surfactant turnover to maintain an appropriate alveolar pool size (homeostasis). Alveolar surfactant can be degraded by macrophages, internalized by type II cells for recycling to lamellar bodies and resecretion, or degraded in lysosomes of type II cells.
Identification of the molecular pathway by which the type II cell “senses” alveolar surfactant pool size and subsequently adjusts surfactant synthesis, secretion, recycling and / or degradation to maintain homeostasis is the major focus of this project.
We have recently identified several novel proteins involved in surfactant phospholipid transport / sensing and are currently generating knockout mice to analyze their function(s).
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