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Internalization of odorant-binding proteins into the mouse olfactory epithelium

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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.

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Acknowledgments

The authors would like to thank Heiko Brose for his initial contribution to the work. We thank Peter Mombaerts, MPI für Biophysik, Frankfurt for providing the OMP-GFP transgenic mice. Shankar Srinivas (Columbia University) kindly provided the ROSA26-EYFP Cre-reporter mice. Purified RAP was a kind donation from Hartwig Schmale, Institut für Biochemie und Molekularbiologie, Universitätsklinikum Hamburg-Eppendorf. This work was supported by the Deutsche Forschungsgemeinschaft.

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Strotmann, J., Breer, H. Internalization of odorant-binding proteins into the mouse olfactory epithelium. Histochem Cell Biol 136, 357–369 (2011). https://doi.org/10.1007/s00418-011-0850-y

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