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      Transcriptomic and Proteomic Profiling Revealed High Proportions of Odorant Binding and Antimicrobial Defense Proteins in Olfactory Tissues of the House Mouse

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          Abstract

          Mammalian olfaction depends on chemosensory neurons of the main olfactory epithelia (MOE), and/or of the accessory olfactory epithelia in the vomeronasal organ (VNO). Thus, we have generated the VNO and MOE transcriptomes and the nasal cavity proteome of the house mouse, Mus musculus musculus. Both transcriptomes had low levels of sexual dimorphisms, while the soluble proteome of the nasal cavity revealed high levels of sexual dimorphism similar to that previously reported in tears and saliva. Due to low levels of sexual dimorphism in the olfactory receptors in MOE and VNO, the sex-specific sensing seems less likely to be dependent on receptor repertoires. However, olfaction may also depend on a continuous removal of background compounds from the sites of detection. Odorant binding proteins (OBPs) are thought to be involved in this process and in our study Obp transcripts were most expressed along other lipocalins (e.g., Lcn13, Lcn14) and antimicrobial proteins. At the level of proteome, OBPs were highly abundant with only few being sexually dimorphic. We have, however, detected the major urinary proteins MUP4 and MUP5 in males and females and the male-biased central/group-B MUPs that were thought to be abundant mainly in the urine. The exocrine gland-secreted peptides ESP1 and ESP22 were male-biased but not male-specific in the nose. For the first time, we demonstrate that the expression of nasal lipocalins correlates with antimicrobial proteins thus suggesting that their individual variation may be linked to evolvable mechanisms that regulate natural microbiota and pathogens that regularly enter the body along the ‘eyes-nose-oral cavity’ axis.

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          Most cited references69

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          Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron.

          Although iron is required to sustain life, its free concentration and metabolism have to be tightly regulated. This is achieved through a variety of iron-binding proteins including transferrin and ferritin. During infection, bacteria acquire much of their iron from the host by synthesizing siderophores that scavenge iron and transport it into the pathogen. We recently demonstrated that enterochelin, a bacterial catecholate siderophore, binds to the host protein lipocalin 2 (ref. 5). Here, we show that this event is pivotal in the innate immune response to bacterial infection. Upon encountering invading bacteria the Toll-like receptors on immune cells stimulate the transcription, translation and secretion of lipocalin 2; secreted lipocalin 2 then limits bacterial growth by sequestrating the iron-laden siderophore. Our finding represents a new component of the innate immune system and the acute phase response to infection.
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            The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition.

            First identified as a neutrophil granule component, neutrophil gelatinase-associated lipocalin (NGAL; also called human neutrophil lipocalin, 24p3, uterocalin, or neu-related lipocalin) is a member of the lipocalin family of binding proteins. Putative NGAL ligands, including neutrophil chemotactic agents such as N-formylated tripeptides, have all been refuted by recent biochemical and structural results. NGAL has subsequently been implicated in diverse cellular processes, but without a characterized ligand, the molecular basis of these functions remained mysterious. Here we report that NGAL tightly binds bacterial catecholate-type ferric siderophores through a cyclically permuted, hybrid electrostatic/cation-pi interaction and is a potent bacteriostatic agent in iron-limiting conditions. We therefore propose that NGAL participates in the antibacterial iron depletion strategy of the innate immune system.
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              A novel multigene family may encode odorant receptors: a molecular basis for odor recognition.

              The mammalian olfactory system can recognize and discriminate a large number of different odorant molecules. The detection of chemically distinct odorants presumably results from the association of odorous ligands with specific receptors on olfactory sensory neurons. To address the problem of olfactory perception at a molecular level, we have cloned and characterized 18 different members of an extremely large multigene family that encodes seven transmembrane domain proteins whose expression is restricted to the olfactory epithelium. The members of this novel gene family are likely to encode a diverse family of odorant receptors.
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                Author and article information

                Contributors
                Journal
                Front Genet
                Front Genet
                Front. Genet.
                Frontiers in Genetics
                Frontiers Media S.A.
                1664-8021
                05 February 2018
                2018
                : 9
                : 26
                Affiliations
                [1]BIOCEV Group, Department of Zoology, Faculty of Science, Charles University , Prague, Czechia
                Author notes

                Edited by: James J. Cai, Texas A&M University, United States

                Reviewed by: Reinaldo A. De Brito, Federal University of São Carlos, Brazil; Robert A. Haney, University of Massachusetts Lowell, United States; Adelino V. M. Canario, University of the Algarve, Portugal

                *Correspondence: Pavel Stopka, pstopka@ 123456natur.cuni.cz

                This article was submitted to Evolutionary and Population Genetics, a section of the journal Frontiers in Genetics

                Article
                10.3389/fgene.2018.00026
                5807349
                29459883
                cb646b1a-f450-478c-a903-a8818b2edef4
                Copyright © 2018 Kuntová, Stopková and Stopka.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 July 2017
                : 22 January 2018
                Page count
                Figures: 5, Tables: 0, Equations: 0, References: 85, Pages: 13, Words: 0
                Funding
                Funded by: European Regional Development Fund 10.13039/501100008530
                Award ID: CZ.1.05/1.1.00/02.0109
                Funded by: Ministerstvo Školství, Mládeže a Tělovýchovy 10.13039/501100001823
                Award ID: NPU II, LQ1604
                Categories
                Genetics
                Original Research

                Genetics
                olfactory,lipocalin,chemical communication,immunity,mup,obp,antimicrobial cationic peptides,evolvability

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