Function of family-C V2R genes: an integrated analysis of DeltaV2R-C mice
Final Report Abstract
At the center of this tandem project was the investigation of a novel subpopulation of sensory neurons in the main olfactory system that express the cation channel Trpc2. Several reports were published on this topic. Together, these investigations make a significant impact on our understanding of the organization of the mammalian sense of smell. We established the existence of Trpc2-expressing cells in the main olfactory system and undertook a detailed molecular profiling of these novel types of sensory neurons. These cell types can be distinguished at the single-cell level by expression of Adcy3: positive, type A and negative, type B. Among MOE cells, type B cells are unique in their expression of the soluble guanylate cyclase Gucy1b2, leading to the generation of a novel Gucy1b2-IRES-tauGFP gene-targeted mouse strain. Furthermore, we discovered that type B cells function as sensitive detectors of low oxygen, and that both Gucy1b2 and Trpc2 are required for cellular Ca2+ responses to low oxygen. As deviations from the initial application, we also investigated the role of H2-Mv genes, a family of nine nonclassical class I major histocompatibility complex genes, in the function of sensory neurons of the vomeronasal organ. In contrast to previous proposals, we found that H2-Mv genes are not absolutely essential for the generation of physiological responses, but are required for ultrasensitive chemodetection by a subset of vomeronasal sensory neurons. Finally, we also embarked on an analysis of the peptidome in mouse urine. These studies succeeded in the first identification of peptides in urine that are normally presented by major histocompatibility complex molecules in the immune system. On the basis of these results, we proposed that urinary peptides represent a real-time sampling of the expressed genome available for chemosensory assessment by other individuals. Together, these investigations provided a rich source of novel findings that advance substantially our understanding of the molecular mechanisms underlying the mammalian sense of smell.
Publications
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(2009) Structural requirements for the activation of vomeronasal sensory neurons by MHC peptides. Nat Neurosci 12, 1551-1558
Leinders-Zufall T, Ishii T, Mombaerts P, Zufall F, Boehm T
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(2012) Mammalian-specific OR37 receptors are differentially activated by distinct odorous fatty aldehydes. Chem Senses 37, 479-493
Bautze V, Bär R, Fissler B, Trapp M, Schmidt D, Beifuss U, Bufe B, Zufall F, Breer H, Strotmann J
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(2013) Mouse urinary peptides provide a molecular basis for genotype discrimination by nasal sensory neurons. Nat Commun 4, 1616
Sturm T, Leinders-Zufall T, Macek B, Walzer M, Jung S, Pömmerl B, Stevanovic S, Zufall F, Overath P, Rammensee HG
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(2014) A family of nonclassical class I MHC genes contributes to ultrasensitive chemodetection by mouse vomeronasal sensory neurons. J Neurosci 34, 5121-5133
Leinders-Zufall T, Ishii T, Chamero P, Hendrix P, Oboti L, Schmid A, Kircher S, Pyrski M, Akiyoshi S, Khan M, Vaes E, Zufall F, Mombaerts P
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(2014) Trpc2-expressing sensory neurons in the main olfactory epithelium of the mouse. Cell Rep 8, 583-595
Omura M, Mombaerts P
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(2015) Trpc2-expressing sensory neurons in the mouse main olfactory epithelium of type B express the soluble guanylate cyclase Gucy1b2. Mol Cell Neurosci 65, 114-124
Omura M, Mombaerts P
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(2016) A sensor for low environmental oxygen in the mouse main olfactory epithelium. Neuron 92, 1196-1203
Bleymehl K, Perez-Gomez A, Omura M, Moreno-Perez A, Macias D, Bai Z, Johnson RS, Leinders-Zufall T, Zufall F, Mombaerts P
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Chemosensory Transduction. The Detection of Odors, Tastes, and Other Chemostimuli (2016). Academic Press. ISBN: 9780128016947
eds. Zufall F, Munger SD
