Abstract
Male house mice produce large quantities of major urinary proteins (MUPs), which function to bind and transport volatile pheromones, though they may also function as scavengers that bind and excrete toxic compounds (‘toxic waste hypothesis’). In this study, we demonstrate the presence of an industrial chemical, 2,4-di-tert-butylphenol (DTBP), in the urine of wild-derived house mice (Mus musculus musculus). Addition of guanidine hydrochloride to male and female urine resulted in an increased release of DTBP. This increase was only observed in the high molecular weight fractions (HMWF; > 3 kDa) separated from male or female urine, suggesting that the increased release of DTBP was likely due to the denaturation of MUPs and the subsequent release of MUP-bound DTBP. Furthermore, when DTBP was added to a HMWF isolated from male urine, an increase in 2-sec-butyl-4,5-dihydrothiazole (SBT), the major ligand of MUPs and a male-specific pheromone, was observed, indicating that DTBP was bound to MUPs and displaced SBT. These results suggest that DTBP is a MUP ligand. Moreover, we found evidence for competitive ligand binding between DTBP and SBT, suggesting that males potentially face a tradeoff between eliminating toxic wastes versus transporting pheromones. Our findings support the hypothesis that MUPs bind and eliminate toxic wastes, which may provide the most important fitness benefits of excreting large quantities of these proteins.
Highlights
Major urinary proteins (MUPs) are members of the lipocalin family that can sequester and transport a variety of lipophilic molecules in blood and other hydrophilic body fluids [1]
The retention time and mass spectrum of DTBP detected in the samples matched those of a synthetic standard, and the mass spectra of DTBP obtained from a male mouse urine sample versus a synthetic standard are shown in Fig 1B and 1C, respectively
The majority of SBT was associated with the high molecular weight fractions (HMWF) obtained from male urine (Fig 3C). These results strongly suggest that DTBP and SBT are largely bound to urinary proteins ( 95% of which are MUPs [19]) present in HMWF and released once the proteins are denatured
Summary
Major urinary proteins (MUPs) are members of the lipocalin family that can sequester and transport a variety of lipophilic molecules in blood and other hydrophilic body fluids [1]. MUPs have been suggested to have a potentially more important function by acting as scavengers that bind and excrete toxic compounds. This ‘toxic waste hypothesis’ has been independently suggested by two different laboratories [5, 6]. It is consistent with the detoxification function of other lipocalins [7] and would help explain why Mup genes are expressed in the liver.
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