Browsing by Subject "Pheromones"
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Item Open Access Mating in wild yeast: delayed interest in sex after spore germination.(Molecular biology of the cell, 2018-12) McClure, Allison W; Jacobs, Katherine C; Zyla, Trevin R; Lew, Daniel JStudies of laboratory strains of Saccharomyces cerevisiae have uncovered signaling pathways involved in mating, including information-processing strategies to optimize decisions to mate or to bud. However, lab strains are heterothallic (unable to self-mate), while wild yeast are homothallic. And while mating of lab strains is studied using cycling haploid cells, mating of wild yeast is thought to involve germinating spores. Thus, it was unclear whether lab strategies would be appropriate in the wild. Here, we have investigated the behavior of several yeast strains derived from wild isolates. Following germination, these strains displayed large differences in their propensity to mate or to enter the cell cycle. The variable interest in sex following germination was correlated with differences in pheromone production, which were due to both cis- and trans-acting factors. Our findings suggest that yeast spores germinating in the wild may often enter the cell cycle and form microcolonies before engaging in mating.Item Open Access Mechanisms that ensure monogamous mating in Saccharomyces cerevisiae.(Molecular biology of the cell, 2021-04) Robertson, Corrina G; Clark-Cotton, Manuella R; Lew, Daniel JHaploid cells of the budding yeast Saccharomyces cerevisiae communicate using secreted pheromones and mate to form diploid zygotes. Mating is monogamous, resulting in the fusion of precisely one cell of each mating type. Monogamous mating in crowded conditions, where cells have access to more than one potential partner, raises the question of how multiple-mating outcomes are prevented. Here we identify mutants capable of mating with multiple partners, revealing the mechanisms that ensure monogamous mating. Before fusion, cells develop polarity foci oriented toward potential partners. Competition between these polarity foci within each cell leads to disassembly of all but one focus, thus favoring a single fusion event. Fusion promotes the formation of heterodimeric complexes between subunits that are uniquely expressed in each mating type. One complex shuts off haploid-specific gene expression, and the other shuts off the ability to respond to pheromone. Zygotes able to form either complex remain monogamous, but zygotes lacking both can re-mate.Item Open Access Mouse Pheromone Receptors: the Molecular Basis of Surface Trafficking and Ligand Selectivity(2009) Dey, SandeepaPheromones are chemicals from conspecifics that affect innate behavior or hormonal changes. In mammals, the vomeronasal organ (VNO) is thought to play a prominent role in detecting pheromones; the vomeronasal sensory neurons (VSNs) express three families of seven-transmembrane G-protein coupled receptors (GPCRs): the V1Rs, V2Rs, and FPRs, in two molecularly and spatially-distinct regions. In mice, VSNs that express the V2Rs are thought to detect peptide cues, including MHC-presenting peptides, major urinary proteins (MUPs), and exocrine gland-secreting peptides (ESPs). They are thought to be involved in various pheromone-mediated behaviors and physiological changes, such as mating, aggression, and selective pregnancy block. In order to understand how pheromones are detected by the vomeronasal receptors, it is essential to know which receptors are activated by a given chemical. However, identifying cognate ligands for the V2Rs has been challenging, partly because they are poorly localized to the surface of heterologous cells. Here, we show that the calreticulin chaperone family members play a crucial role in trafficking V2Rs. A calreticulin homologue, calreticulin4 is specifically expressed in the VNO, while calreticulin expression level is low. Depleting calreticulin expression in HEK293T cells allows V2Rs to be trafficked to the cell surface, whereas expression of calreticulin4 does not block the trafficking of the V2Rs. Using this knowledge, we have established a heterologous cell system to functionally identify the V2Rs and demonstrate that the ESP family members can differentially activate the V2Rs. We also show the large extracellular domain of the V2Rs plays a crucial role in ligand selectivity. Our results provide a platform to characterize ligand selectivity of the V2Rs and suggest that a unique mechanism involving calreticulins regulates the functional expression of the V2Rs.
Item Open Access Ratiometric GPCR signaling enables directional sensing in yeast.(PLoS biology, 2019-10-17) Henderson, Nicholas T; Pablo, Michael; Ghose, Debraj; Clark-Cotton, Manuella R; Zyla, Trevin R; Nolen, James; Elston, Timothy C; Lew, Daniel JAccurate detection of extracellular chemical gradients is essential for many cellular behaviors. Gradient sensing is challenging for small cells, which can experience little difference in ligand concentrations on the up-gradient and down-gradient sides of the cell. Nevertheless, the tiny cells of the yeast Saccharomyces cerevisiae reliably decode gradients of extracellular pheromones to find their mates. By imaging the behavior of polarity factors and pheromone receptors, we quantified the accuracy of initial polarization during mating encounters. We found that cells bias the orientation of initial polarity up-gradient, even though they have unevenly distributed receptors. Uneven receptor density means that the gradient of ligand-bound receptors does not accurately reflect the external pheromone gradient. Nevertheless, yeast cells appear to avoid being misled by responding to the fraction of occupied receptors rather than simply the concentration of ligand-bound receptors. Such ratiometric sensing also serves to amplify the gradient of active G protein. However, this process is quite error-prone, and initial errors are corrected during a subsequent indecisive phase in which polarity clusters exhibit erratic mobile behavior.Item Open Access Responses to conspecific chemical stimuli in the treatment snail Achatina fulica (Pulmonata: Sigmurethra).(Behavioral biology, 1978-03) Chase, R; Pryer, K; Baker, R; Madison, DThe giant African snail, Achatina fulica, followed trails made with the mucus of A. fulica, but did not follow those consisting of mucus from Otala vermiculata. In olfactometer experiments, A. fulica and Helix aperta oriented preferentially toward the odor of their own species when both odors were presented simultaneously. Species specificity was less pronounced when the odor of O. vermiculata was paired with either of the other two snail odors. Sexually mature A. fulica that had been housed individually for 30 days prior to testing followed mucus trails better than did similar snails housed collectively. Immature A. fulica did not follow trails better after isolation, but showed a facilitative effect of isolation on conspecific orientation in the olfactometer. Three-week-old snails, maintained in individual containers from the time of hatching, also oriented preferentially toward conspecific odors. © 1978 Academic Press, Inc.Item Open Access Succinylated octopamine ascarosides and a new pathway of biogenic amine metabolism in Caenorhabditis elegans.(J Biol Chem, 2013-06-28) Artyukhin, Alexander B; Yim, Joshua J; Srinivasan, Jagan; Izrayelit, Yevgeniy; Bose, Neelanjan; von Reuss, Stephan H; Jo, Yeara; Jordan, James M; Baugh, L Ryan; Cheong, Micheong; Sternberg, Paul W; Avery, Leon; Schroeder, Frank CThe ascarosides, small-molecule signals derived from combinatorial assembly of primary metabolism-derived building blocks, play a central role in Caenorhabditis elegans biology and regulate many aspects of development and behavior in this model organism as well as in other nematodes. Using HPLC-MS/MS-based targeted metabolomics, we identified novel ascarosides incorporating a side chain derived from succinylation of the neurotransmitter octopamine. These compounds, named osas#2, osas#9, and osas#10, are produced predominantly by L1 larvae, where they serve as part of a dispersal signal, whereas these ascarosides are largely absent from the metabolomes of other life stages. Investigating the biogenesis of these octopamine-derived ascarosides, we found that succinylation represents a previously unrecognized pathway of biogenic amine metabolism. At physiological concentrations, the neurotransmitters serotonin, dopamine, and octopamine are converted to a large extent into the corresponding succinates, in addition to the previously described acetates. Chemically, bimodal deactivation of biogenic amines via acetylation and succinylation parallels posttranslational modification of proteins via acetylation and succinylation of L-lysine. Our results reveal a small-molecule connection between neurotransmitter signaling and interorganismal regulation of behavior and suggest that ascaroside biosynthesis is based in part on co-option of degradative biochemical pathways.