title: Loss of the V-ATPase B1 subunit isoform expressed in non-neuronal cells of the mouse olfactory epithelium impairs olfactory function.
abstract: The vacuolar proton-pumping ATPase (V-ATPase) is the main mediator of intracellular organelle acidification and also regulates transmembrane proton (H(+)) secretion, which is necessary for an array of physiological functions fulfilled by organs such as the kidney, male reproductive tract, lung, bone, and ear. In this study we characterize expression of the V-ATPase in the main olfactory epithelium of the mouse, as well as a functional role for the V-ATPase in odor detection. We report that the V-ATPase localizes to the apical membrane microvilli of olfactory sustentacular cells and to the basolateral membrane of microvillar cells. Plasma membrane V-ATPases containing the B1 subunit isoform are not detected in olfactory sensory neurons or in the olfactory bulb. This precise localization of expression affords the opportunity to ascertain the functional relevance of V-ATPase expression upon innate, odor-evoked behaviors in B1-deficient mice. This animal model exhibits diminished innate avoidance behavior (revealed as a decrease in freezing time and an increase in the number of sniffs in the presence of trimethyl-thiazoline) and diminished innate appetitive behavior (a decrease in time spent investigating the urine of the opposite sex). We conclude that V-ATPase-mediated H(+) secretion in the olfactory epithelium is required for optimal olfactory function.
authors.affiliation: MGH Center for Systems Biology, Division of Nephrology, Massachusetts General Hospital, Boston, Massachusetts, United States of America. Paunescu.Teodor@mgh.harvard.edu
authors.forename: Teodor G
authors.initials: TG
authors.lastname: Păunescu
authors.forename: Steven
authors.initials: S
authors.lastname: Rodriguez
authors.forename: Eric
authors.initials: E
authors.lastname: Benz
authors.forename: Mary
authors.initials: M
authors.lastname: McKee
authors.forename: Robert
authors.initials: R
authors.lastname: Tyszkowski
authors.forename: Mark W
authors.initials: MW
authors.lastname: Albers
authors.forename: Dennis
authors.initials: D
authors.lastname: Brown
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D008871:Microvilli / Q000378:metabolism; D009812:Odorants; D009830:Olfactory Bulb / Q000166:cytology*; D009831:Olfactory Mucosa / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism*; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D025262:Vacuolar Proton-Translocating ATPases