Regulation of water permeability across epithelial and endothelial membranes is essential to normal organ function, however the molecular determinants of that process at many sites remain incompletely defined. Aquaporins are membrane channel proteins with highly selective permeability…
more characteristics; several members of the aquaporin protein family are permeated only by water. The clinical significance of these proteins was amplified by our identification of decreased urinary concentration and pulmonary vascular permeability in rare aquaporin-1 (AQP1) null humans. Following definition of the ontogeny and distribution of aquaporins in the respiratory tract, our group has focused on aquaporin regulation and function in normal and pathophysiologic conditions. Our studies of AQP1, present in endothelium and select epithelial cells, and AQP5, present in secretory glands and respiratory epithelium, revealed dynamic regulation of protein abundance and distribution through a combination of transcriptional and post-translational mechanisms. Most recently, we have identified that aquaporin abundance is closely coupled to extracellular osmolality: hypertonicity increases protein abundance via activation of epidermal growth factor receptor isoforms, and hypotonicity rapidly decreases aquaporin abundance in a process that requires activation of the cation channel transient receptor potential vanilloid-4 (TRPV4). We believe these studies will provide novel insights into mechanisms of membrane water homeostasis that will identify aquaporins as distinct targets for therapy in diseases of altered fluid homeostasis.
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