title: Internalization of odorant-binding proteins into the mouse olfactory epithelium.
abstract: The detection of odorants in vertebrates is mediated by chemosensory neurons that reside in the olfactory epithelium of the nose. In land-living species, the hydrophobic odorous compounds inhaled by the airstream are dissolved in the nasal mucus by means of specialized globular proteins, the odorant-binding proteins (OBPs). To assure the responsiveness to odors of each inhalation, a rapid removal of odorants from the microenvironment of the receptor is essential. In order to follow the fate of OBP/odorant complexes, a recombinant OBP was fluorescently labeled, loaded with odorous compounds, and applied to the nose of a mouse. Very quickly, labeled OBP appeared inside the sustentacular cells of the epithelium. This uptake occurred only when the OBP was loaded with appropriate odorant compounds. A search for candidate transporters that could mediate such an uptake process led to the identification of the low density lipoprotein receptor Lrp2/Megalin. In the olfactory epithelium, megalin was found to be specifically expressed in sustentacular cells and the Megalin protein was located in their microvilli. In vitro studies using a cell line that expresses megalin revealed a rapid internalization of OBP/odorant complexes into lysosomes. The uptake was blocked by a Megalin inhibitor, as was the internalization of OBPs into the sustentacular cells of the olfactory epithelium. The results suggest that a Megalin-mediated internalization of OBP/odorant complexes into the sustentacular cells may represent an important mechanism for a rapid and local clearance of odorants.
authors.affiliation: Institute of Physiology, University of Hohenheim, Stuttgart, Germany. strotman@uni-hohenheim.de
authors.forename: Jörg
authors.initials: J
authors.lastname: Strotmann
authors.forename: Heinz
authors.initials: H
authors.lastname: Breer
mesh_terms: D000818:Animals; D002460:Cell Line; D004285:Dogs; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009831:Olfactory Mucosa / Q000378:metabolism*; D018035:Receptors, Odorant / Q000378:metabolism*; D012903:Smell / Q000502:physiology
chemical_list: D026561:Low Density Lipoprotein Receptor-Related Protein-2; C055127:Lrp2 protein, mouse; D018035:Receptors, Odorant; C045648:odorant-binding protein