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Keywords = yeast pheromone

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14 pages, 1623 KiB  
Article
Mating Disruption of Helicoverpa armigera (Lepidoptera: Noctuidae) Using Yeast-Derived Pheromones in Cotton Fields
by Dimitris Raptopoulos, Petri-Christina Betsi, Neoklis Manikas, Irina Borodina and Maria Konstantopoulou
Insects 2025, 16(5), 523; https://doi.org/10.3390/insects16050523 - 15 May 2025
Viewed by 1035
Abstract
The use of insect sex pheromones as an alternative technology for pest control in agriculture and forestry offers a promising solution. The development of a novel technology for the biological production of pheromones through yeast fermentation significantly lowers production costs, enabling the adoption [...] Read more.
The use of insect sex pheromones as an alternative technology for pest control in agriculture and forestry offers a promising solution. The development of a novel technology for the biological production of pheromones through yeast fermentation significantly lowers production costs, enabling the adoption of sustainable pest control practices in field crops, a strategy previously reserved for high-value crops. Over three years of monitoring and mating disruption trials in Greek cotton fields, focusing on the cotton bollworm Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae), it was confirmed that yeast-derived pheromones exhibit equal efficacy compared to their chemically synthesized counterparts. For the mating disruption of H. armigera, a biodegradable, flowable, and paraffin-based matrix was developed. The matrix adheres to plants, protects the labile pheromone molecules (Z)-11-hexadecenal and (Z)-9-hexadecenal, and controls their gradual release into the environment. These biodegradable polymer blobs act as non-retrievable dispensers and can be deployed manually or via unmanned aerial vehicles (UAVs), ensuring efficient and accurate application. This precise, time-efficient, and economically sound technology aligns with European Commission initiatives, such as the Green Deal’s Farm to Fork Strategy and the Biodiversity Strategy, contributing to food sustainability while respecting biodiversity. Full article
(This article belongs to the Special Issue Natural Metabolites as Biocontrol Agents of Insect Pests)
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11 pages, 2720 KiB  
Article
Septin Defects Favour Symmetric Inheritance of the Budding Yeast Deceptive Courtship Memory
by Fozia Akhtar, Bastien Brignola and Fabrice Caudron
Int. J. Mol. Sci. 2023, 24(3), 3003; https://doi.org/10.3390/ijms24033003 - 3 Feb 2023
Cited by 1 | Viewed by 1846
Abstract
Mnemons are prion-like elements that encode cellular memories of past cellular adaptations and do not spread to progenies during cell divisions. During the deceptive courtship in budding yeast, the Whi3 mnemon (Whi3mnem) condenses into a super-assembly to encode a mating pheromone [...] Read more.
Mnemons are prion-like elements that encode cellular memories of past cellular adaptations and do not spread to progenies during cell divisions. During the deceptive courtship in budding yeast, the Whi3 mnemon (Whi3mnem) condenses into a super-assembly to encode a mating pheromone refractory state established in the mother cell. Whi3mnem is confined to the mother cell such that their daughter cells have the ability to respond to the mating pheromone. Confinement of Whi3mnem involves its association with the endoplasmic reticulum membranes and the compartmentalization of these membranes by the lateral membrane diffusion barrier at the bud neck, the limit between the mother cell and the bud. However, during the first cell division after the establishment of the pheromone refractory state, this adaptation is more likely to be inherited by the daughter cell than in subsequent cell divisions. Here, we show that the first cell division is associated with larger daughter cells and cytokinesis defects, traits that are not observed in subsequent cell divisions. The cytoskeletal septin protein shows aberrant localisation in these divisions and the septin-dependent endoplasmic reticulum membrane diffusion barrier is weakened. Overall, these data suggest that cytokinesis defects associated with prolonged cell division can alter the confinement and inheritance pattern of a cellular memory. Full article
(This article belongs to the Special Issue Protein-Based Infection, Inheritance, and Memory)
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27 pages, 4159 KiB  
Review
Comparison of Experimental Approaches Used to Determine the Structure and Function of the Class D G Protein-Coupled Yeast α-Factor Receptor
by Mark E. Dumont and James B. Konopka
Biomolecules 2022, 12(6), 761; https://doi.org/10.3390/biom12060761 - 30 May 2022
Cited by 3 | Viewed by 2746
Abstract
The Saccharomyces cerevisiae α-factor mating pheromone receptor (Ste2p) has been studied as a model for the large medically important family of G protein-coupled receptors. Diverse yeast genetic screens and high-throughput mutagenesis of STE2 identified a large number of loss-of-function, constitutively-active, dominant-negative, and intragenic [...] Read more.
The Saccharomyces cerevisiae α-factor mating pheromone receptor (Ste2p) has been studied as a model for the large medically important family of G protein-coupled receptors. Diverse yeast genetic screens and high-throughput mutagenesis of STE2 identified a large number of loss-of-function, constitutively-active, dominant-negative, and intragenic second-site suppressor mutants as well as mutations that specifically affect pheromone binding. Facile genetic manipulation of Ste2p also aided in targeted biochemical approaches, such as probing the aqueous accessibility of substituted cysteine residues in order to identify the boundaries of the seven transmembrane segments, and the use of cysteine disulfide crosslinking to identify sites of intramolecular contacts in the transmembrane helix bundle of Ste2p and sites of contacts between the monomers in a Ste2p dimer. Recent publication of a series of high-resolution cryo-EM structures of Ste2p in ligand-free, agonist-bound and antagonist-bound states now makes it possible to evaluate the results of these genetic and biochemical strategies, in comparison to three-dimensional structures showing activation-related conformational changes. The results indicate that the genetic and biochemical strategies were generally effective, and provide guidance as to how best to apply these experimental strategies to other proteins. These strategies continue to be useful in defining mechanisms of signal transduction in the context of the available structures and suggest aspects of receptor function beyond what can be discerned from the available structures. Full article
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17 pages, 3938 KiB  
Article
Cla4p Kinase Activity Is Down-Regulated by Fus3p during Yeast Mating
by Junwon Kim and Mark D. Rose
Biomolecules 2022, 12(4), 598; https://doi.org/10.3390/biom12040598 - 18 Apr 2022
Cited by 4 | Viewed by 2543
Abstract
In Saccharomyces cerevisiae, the p21-activated kinase Cla4p regulates polarized morphogenesis and cytokinesis. However, it remains unknown how Cla4p kinase activity is regulated. After pheromone exposure, yeast cells temporally separate the mitotic and mating programs by sequestering Fus2p in the nucleus until cell [...] Read more.
In Saccharomyces cerevisiae, the p21-activated kinase Cla4p regulates polarized morphogenesis and cytokinesis. However, it remains unknown how Cla4p kinase activity is regulated. After pheromone exposure, yeast cells temporally separate the mitotic and mating programs by sequestering Fus2p in the nucleus until cell cycle completion, after which Fus2p exits to facilitate cell fusion. Previously, we showed that sequestration is regulated by two opposing protein kinases, Cla4p and Fus3p. Phosphorylation of Fus2p-S67 by Cla4p promotes nuclear localization by both activating nuclear import and blocking export. During mating, phosphorylation of Fus2p-S85 and Fus2p-S100 by Fus3p promotes nuclear export and blocks import. Here, we find that Cla4p kinase activity is itself down-regulated during mating. Pheromone exposure causes Cla4p hyper-phosphorylation and reduced Fus2p-S67 phosphorylation, dependent on Fus3p. Multiple phosphorylation sites in Cla4p are mating- and/or Fus3p-specific. Of these, Cla4p-S186 phosphorylation reduced the kinase activity of Cla4p, in vitro. A phosphomimetic cla4-S186E mutation caused a strong reduction in Fus2p-S67 phosphorylation and nuclear localization, in vivo. More generally, a non-phosphorylatable mutation, cla4-S186A, caused failure to maintain pheromone arrest and delayed formation of the mating-specific septin morphology. Thus, as cells enter the mating pathway, Fus3p counteracts Cla4p kinase activity to allow proper mating differentiation. Full article
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16 pages, 3203 KiB  
Article
Microfluidic-Enabled Multi-Cell-Densities-Patterning and Culture Device for Characterization of Yeast Strains’ Growth Rates under Mating Pheromone
by Jing Zhang, Wenting Shen, Zhiyuan Cai, Kaiyue Chen, Qi Ouyang, Ping Wei, Wei Yang and Chunxiong Luo
Chemosensors 2022, 10(4), 141; https://doi.org/10.3390/chemosensors10040141 - 8 Apr 2022
Cited by 2 | Viewed by 2956
Abstract
Yeast studies usually focus on exploring diversity in terms of a specific trait (such as growth rate, antibiotic resistance, or fertility) among extensive strains. Microfluidic chips improve these biological studies in a manner of high throughput and high efficiency. For a population study [...] Read more.
Yeast studies usually focus on exploring diversity in terms of a specific trait (such as growth rate, antibiotic resistance, or fertility) among extensive strains. Microfluidic chips improve these biological studies in a manner of high throughput and high efficiency. For a population study of yeast, it is of great significance to set a proper initial cell density for every strain under specific circumstances. Herein, we introduced a novel design of chip, which enables users to load cells in a gradient order (six alternatives) of initial cell density within one channel. We discussed several guidelines to choose the appropriate chamber to ensure successful data recording. With this chip, we successfully studied the growth rate of yeast strains under a mating response, which is crucial for yeasts to control growth behaviors for prosperous mating. We investigated the growth rate of eight different yeast strains under three different mating pheromone levels (0.3 μM, 1 μM, and 10 μM). Strains with, even, a six-fold in growth rate can be recorded, with the available data produced simultaneously. This work has provided an efficient and time-saving microfluidic platform, which enables loading cells in a pattern of multi-cell densities for a yeast population experiment, especially for a high-throughput study. Besides, a quantitatively analyzed growth rate of different yeast strains shall reveal inspiring perspectives for studies concerning yeast population behavior with a stimulated mating pheromone. Full article
(This article belongs to the Special Issue Microfluidic Devices for Biological Quantitative Analysis)
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13 pages, 1833 KiB  
Article
Pheromone Guidance of Polarity Site Movement in Yeast
by Katherine C. Jacobs and Daniel J. Lew
Biomolecules 2022, 12(4), 502; https://doi.org/10.3390/biom12040502 - 26 Mar 2022
Cited by 4 | Viewed by 2907
Abstract
Cells’ ability to track chemical gradients is integral to many biological phenomena, including fertilization, development, accessing nutrients, and combating infection. Mating of the yeast Saccharomyces cerevisiae provides a tractable model to understand how cells interpret the spatial information in chemical gradients. Mating yeast [...] Read more.
Cells’ ability to track chemical gradients is integral to many biological phenomena, including fertilization, development, accessing nutrients, and combating infection. Mating of the yeast Saccharomyces cerevisiae provides a tractable model to understand how cells interpret the spatial information in chemical gradients. Mating yeast of the two different mating types secrete distinct peptide pheromones, called a-factor and α-factor, to communicate with potential partners. Spatial gradients of pheromones are decoded to guide mobile polarity sites so that polarity sites in mating partners align towards each other, as a prerequisite for cell-cell fusion and zygote formation. In ascomycetes including S. cerevisiae, one pheromone is prenylated (a-factor) while the other is not (α-factor). The difference in physical properties between the pheromones, combined with associated differences in mechanisms of secretion and extracellular pheromone metabolism, suggested that the pheromones might differ in the spatial information that they convey to potential mating partners. However, as mating appears to be isogamous in this species, it is not clear why any such signaling difference would be advantageous. Here we report assays that directly track movement of the polarity site in each partner as a way to understand the spatial information conveyed by each pheromone. Our findings suggest that both pheromones convey very similar information. We speculate that the different pheromones were advantageous in ancestral species with asymmetric mating systems and may represent an evolutionary vestige in yeasts that mate isogamously. Full article
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12 pages, 1138 KiB  
Review
The Path to Therapeutic Furin Inhibitors: From Yeast Pheromones to SARS-CoV-2
by Gary Thomas, Frédéric Couture and Anna Kwiatkowska
Int. J. Mol. Sci. 2022, 23(7), 3435; https://doi.org/10.3390/ijms23073435 - 22 Mar 2022
Cited by 16 | Viewed by 4761
Abstract
The spurious acquisition and optimization of a furin cleavage site in the SARS-CoV-2 spike protein is associated with increased viral transmission and disease, and has generated intense interest in the development and application of therapeutic furin inhibitors to thwart the COVID-19 pandemic. This [...] Read more.
The spurious acquisition and optimization of a furin cleavage site in the SARS-CoV-2 spike protein is associated with increased viral transmission and disease, and has generated intense interest in the development and application of therapeutic furin inhibitors to thwart the COVID-19 pandemic. This review summarizes the seminal studies that informed current efforts to inhibit furin. These include the convergent efforts of endocrinologists, virologists, and yeast geneticists that, together, culminated in the discovery of furin. We describe the pioneering biochemical studies which led to the first furin inhibitors that were able to block the disease pathways which are broadly critical for pathogen virulence, tumor invasiveness, and atherosclerosis. We then summarize how these studies subsequently informed current strategies leading to the development of small-molecule furin inhibitors as potential therapies to combat SARS-CoV-2 and other diseases that rely on furin for their pathogenicity and progression. Full article
(This article belongs to the Special Issue Therapeutic Targeting of the Proteolytic Enzymes)
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11 pages, 1071 KiB  
Article
Cryptococcus neoformans VNII as the Main Cause of Cryptococcosis in Domestic Cats from Rio de Janeiro, Brazil
by Rosani Santos Reis, Isabel Cristina Fábregas Bonna, Isabela Maria da Silva Antonio, Sandro Antonio Pereira, Carlos Roberto Sobrinho do Nascimento, Fausto Klabund Ferraris, Fábio Brito-Santos, Isabella Dib Ferreira Gremião and Luciana Trilles
J. Fungi 2021, 7(11), 980; https://doi.org/10.3390/jof7110980 - 18 Nov 2021
Cited by 10 | Viewed by 3099
Abstract
Cryptococcosis is a systemic fungal disease acquired from contaminated environments with propagules of the basidiomycetous yeasts of the Cryptococcus neoformans and C. gattii species complexes. The C. neoformans species complex classically comprises four major molecular types (VNI, VNII, VNIII, and VNIV), and the [...] Read more.
Cryptococcosis is a systemic fungal disease acquired from contaminated environments with propagules of the basidiomycetous yeasts of the Cryptococcus neoformans and C. gattii species complexes. The C. neoformans species complex classically comprises four major molecular types (VNI, VNII, VNIII, and VNIV), and the C. gattii species complex comprises another four (VGI, VGII, VGIII, and VGIV) and the newly identified molecular type VGV. These major molecular types differ in their epidemiological and ecological features, clinical presentations, and therapeutic outcomes. Generally, the most common isolated types are VNI, VGI, and VGII. The epidemiological profile of cryptococcosis in domestic cats is poorly studied and cats can be the sentinels for human infections. Therefore, the present study aimed to determine the molecular characterization of Cryptococcus spp. isolated from domestic cats and their dwellings in the metropolitan area of Rio de Janeiro, Brazil. A total of 36 Cryptococcus spp. strains, both clinical and environmental, from 19 cats were subtyped using multilocus sequence typing (MLST). The ploidy was identified using flow cytometry and the mating type was determined through amplification with specific pheromone primers. All strains were mating type alpha and 6/36 were diploid (all VNII). Most isolates (63.88%) were identified as VNII, a rare molecular type, leading to the consideration that this genotype is more likely related to skin lesions, since there was a high percentage (68.75%) of cats with skin lesions, which is also considered rare. Further studies regarding the molecular epidemiology of cryptococcosis in felines are still needed to clarify the reason for the large proportion of the rare molecular type VNII causing infections in cats. Full article
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26 pages, 6249 KiB  
Article
Cdc42-Specific GTPase-Activating Protein Rga1 Squelches Crosstalk between the High-Osmolarity Glycerol (HOG) and Mating Pheromone Response MAPK Pathways
by Jesse C. Patterson, Louise S. Goupil and Jeremy Thorner
Biomolecules 2021, 11(10), 1530; https://doi.org/10.3390/biom11101530 - 17 Oct 2021
Cited by 5 | Viewed by 4623
Abstract
Eukaryotes utilize distinct mitogen/messenger-activated protein kinase (MAPK) pathways to evoke appropriate responses when confronted with different stimuli. In yeast, hyperosmotic stress activates MAPK Hog1, whereas mating pheromones activate MAPK Fus3 (and MAPK Kss1). Because these pathways share several upstream components, including the small [...] Read more.
Eukaryotes utilize distinct mitogen/messenger-activated protein kinase (MAPK) pathways to evoke appropriate responses when confronted with different stimuli. In yeast, hyperosmotic stress activates MAPK Hog1, whereas mating pheromones activate MAPK Fus3 (and MAPK Kss1). Because these pathways share several upstream components, including the small guanosine-5'-triphosphate phosphohydrolase (GTPase) cell-division-cycle-42 (Cdc42), mechanisms must exist to prevent inadvertent cross-pathway activation. Hog1 activity is required to prevent crosstalk to Fus3 and Kss1. To identify other factors required to maintain signaling fidelity during hypertonic stress, we devised an unbiased genetic selection for mutants unable to prevent such crosstalk even when active Hog1 is present. We repeatedly isolated truncated alleles of RGA1, a Cdc42-specific GTPase-activating protein (GAP), each lacking its C-terminal catalytic domain, that permit activation of the mating MAPKs under hyperosmotic conditions despite Hog1 being present. We show that Rga1 down-regulates Cdc42 within the high-osmolarity glycerol (HOG) pathway, but not the mating pathway. Because induction of mating pathway output via crosstalk from the HOG pathway takes significantly longer than induction of HOG pathway output, our findings suggest that, under normal conditions, Rga1 contributes to signal insulation by limiting availability of the GTP-bound Cdc42 pool generated by hypertonic stress. Thus, Rga1 action contributes to squelching crosstalk by imposing a type of “kinetic proofreading”. Although Rga1 is a Hog1 substrate in vitro, we eliminated the possibility that its direct Hog1-mediated phosphorylation is necessary for its function in vivo. Instead, we found first that, like its paralog Rga2, Rga1 is subject to inhibitory phosphorylation by the S. cerevisiae cyclin-dependent protein kinase 1 (Cdk1) ortholog Cdc28 and that hyperosmotic shock stimulates its dephosphorylation and thus Rga1 activation. Second, we found that Hog1 promotes Rga1 activation by blocking its Cdk1-mediated phosphorylation, thereby allowing its phosphoprotein phosphatase 2A (PP2A)-mediated dephosphorylation. These findings shed light on why Hog1 activity is required to prevent crosstalk from the HOG pathway to the mating pheromone response pathway. Full article
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15 pages, 2579 KiB  
Article
Post-Transcriptional Control of Mating-Type Gene Expression during Gametogenesis in Saccharomyces cerevisiae
by Randi Yeager, G. Guy Bushkin, Emily Singer, Rui Fu, Benjamin Cooperman and Michael McMurray
Biomolecules 2021, 11(8), 1223; https://doi.org/10.3390/biom11081223 - 17 Aug 2021
Cited by 2 | Viewed by 4308
Abstract
Gametogenesis in diploid cells of the budding yeast Saccharomyces cerevisiae produces four haploid meiotic products called spores. Spores are dormant until nutrients trigger germination, when they bud asexually or mate to return to the diploid state. Each sporulating diploid produces a mix of [...] Read more.
Gametogenesis in diploid cells of the budding yeast Saccharomyces cerevisiae produces four haploid meiotic products called spores. Spores are dormant until nutrients trigger germination, when they bud asexually or mate to return to the diploid state. Each sporulating diploid produces a mix of spores of two haploid mating types, a and α. In asexually dividing haploids, the mating types result from distinct, mutually exclusive gene expression programs responsible for production of mating pheromones and the receptors to sense them, all of which are silent in diploids. It was assumed that spores only transcribe haploid- and mating-type-specific genes upon germination. We find that dormant spores of each mating type harbor transcripts representing all these genes, with the exception of Mata1, which we found to be enriched in a spores. Mata1 transcripts, from a rare yeast gene with two introns, were mostly unspliced. If the retained introns reflect tethering to the MATa locus, this could provide a mechanism for biased inheritance. Translation of pheromones and receptors were repressed at least until germination. We find antisense transcripts to many mating genes that may be responsible. These findings add to the growing number of examples of post-transcriptional regulation of gene expression during gametogenesis. Full article
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24 pages, 2028 KiB  
Article
Dielectric Spectroscopy Based Detection of Specific and Nonspecific Cellular Mechanisms
by Michael R. Stoneman and Valerică Raicu
Sensors 2021, 21(9), 3177; https://doi.org/10.3390/s21093177 - 3 May 2021
Cited by 4 | Viewed by 3260
Abstract
Using radiofrequency dielectric spectroscopy, we have investigated the impact of the interaction between a G protein-coupled receptor (GPCR), the sterile2 α-factor receptor protein (Ste2), and its cognate agonist ligand, the α-factor pheromone, on the dielectric properties of the plasma membrane in living yeast [...] Read more.
Using radiofrequency dielectric spectroscopy, we have investigated the impact of the interaction between a G protein-coupled receptor (GPCR), the sterile2 α-factor receptor protein (Ste2), and its cognate agonist ligand, the α-factor pheromone, on the dielectric properties of the plasma membrane in living yeast cells (Saccharomyces cerevisiae). The dielectric properties of a cell suspension containing a saturating concentration of α-factor were measured over the frequency range 40Hz–110 MHz and compared to the behavior of a similarly prepared suspension of cells in the absence of α-factor. A spherical three-shell model was used to determine the electrical phase parameters for the yeast cells in both types of suspensions. The relative permittivity of the plasma membrane showed a significant increase after exposure to α-factor (by 0.06 ± 0.05). The equivalent experiment performed on yeast cells lacking the ability to express Ste2 showed no change in plasma membrane permittivity. Interestingly, a large change also occurred to the electrical properties of the cellular interior after the addition of α-factor to the cell suspending medium, whether or not the cells were expressing Ste2. We present a number of different complementary experiments performed on the yeast to support these dielectric data and interpret the results in terms of specific cellular reactions to the presence of α-factor. Full article
(This article belongs to the Special Issue Dielectric Spectroscopy Sensors)
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15 pages, 3646 KiB  
Article
Elevated Sporulation Efficiency in Fission Yeast Schizosaccharomyces japonicus Strains Isolated from Drosophila
by Taisuke Seike, Natsue Sakata, Fumio Matsuda and Chikara Furusawa
J. Fungi 2021, 7(5), 350; https://doi.org/10.3390/jof7050350 - 29 Apr 2021
Cited by 14 | Viewed by 3909
Abstract
The fission yeast Schizosaccharomyces japonicus, comprising S. japonicus var. japonicus and S. japonicus var. versatilis varieties, has unique characteristics such as striking hyphal growth not seen in other Schizosaccharomyces species; however, information on its diversity and evolution, in particular mating and sporulation, [...] Read more.
The fission yeast Schizosaccharomyces japonicus, comprising S. japonicus var. japonicus and S. japonicus var. versatilis varieties, has unique characteristics such as striking hyphal growth not seen in other Schizosaccharomyces species; however, information on its diversity and evolution, in particular mating and sporulation, remains limited. Here we compared the growth and mating phenotypes of 17 wild strains of S. japonicus, including eight S. japonicus var. japonicus strains newly isolated from an insect (Drosophila). Unlike existing wild strains isolated from fruits/plants, the strains isolated from Drosophila sporulated at high frequency even under nitrogen-abundant conditions. In addition, one of the strains from Drosophila was stained by iodine vapor, although the type strain of S. japonicus var. japonicus is not stained. Sequence analysis further showed that the nucleotide and amino acid sequences of pheromone-related genes have diversified among the eight strains from Drosophila, suggesting crossing between S. japonicus cells of different genetic backgrounds occurs frequently in this insect. Much of yeast ecology remains unclear, but our findings suggest that insects such as Drosophila might be a good niche for mating and sporulation, and will provide a basis for the understanding of sporulation mechanisms via signal transduction, as well as the ecology and evolution of yeast. Full article
(This article belongs to the Special Issue Signal Transductions in Fungi)
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21 pages, 3482 KiB  
Article
The Specificity of Downstream Signaling for A1 and A2AR Does Not Depend on the C-Terminus, Despite the Importance of This Domain in Downstream Signaling Strength
by Abhinav R. Jain, Claire McGraw and Anne S. Robinson
Biomedicines 2020, 8(12), 603; https://doi.org/10.3390/biomedicines8120603 - 13 Dec 2020
Cited by 5 | Viewed by 3004
Abstract
Recent efforts to determine the high-resolution crystal structures for the adenosine receptors (A1R and A2AR) have utilized modifications to the native receptors in order to facilitate receptor crystallization and structure determination. One common modification is a truncation of the [...] Read more.
Recent efforts to determine the high-resolution crystal structures for the adenosine receptors (A1R and A2AR) have utilized modifications to the native receptors in order to facilitate receptor crystallization and structure determination. One common modification is a truncation of the unstructured C-terminus, which has been utilized for all the adenosine receptor crystal structures obtained to date. Ligand binding for this truncated receptor has been shown to be similar to full-length receptor for A2AR. However, the C-terminus has been identified as a location for protein-protein interactions that may be critical for the physiological function of these important drug targets. We show that variants with A2AR C-terminal truncations lacked cAMP-linked signaling compared to the full-length receptor constructs transfected into mammalian cells (HEK-293). In addition, we show that in a humanized yeast system, the absence of the full-length C-terminus affected downstream signaling using a yeast MAPK response-based fluorescence assay, though full-length receptors showed native-like G-protein coupling. To further study the G protein coupling, we used this humanized yeast platform to explore coupling to human-yeast G-protein chimeras in a cellular context. Although the C-terminus was essential for Gα protein-associated signaling, chimeras of A1R with a C-terminus of A2AR coupled to the A1R-specific Gα (i.e., Gαi1 versus Gαs). This surprising result suggests that the C-terminus is important in the signaling strength, but not specificity, of the Gα protein interaction. This result has further implications in drug discovery, both in enabling the experimental use of chimeras for ligand design, and in the cautious interpretation of structure-based drug design using truncated receptors. Full article
(This article belongs to the Special Issue Advances in Adenosine Receptor Research)
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15 pages, 4540 KiB  
Article
The Untapped Australasian Diversity of Astaxanthin-Producing Yeasts with Biotechnological Potential—Phaffia australis sp. nov. and Phaffia tasmanica sp. nov.
by Márcia David-Palma, Diego Libkind, Patrícia H. Brito, Margarida Silva, Nicolás Bellora, Marco A. Coelho, Joseph Heitman, Paula Gonçalves and José Paulo Sampaio
Microorganisms 2020, 8(11), 1651; https://doi.org/10.3390/microorganisms8111651 - 24 Oct 2020
Cited by 13 | Viewed by 3612
Abstract
Phaffia is an orange-colored basidiomycetous yeast genus of the order Cystofilobasidiales that contains a single species, P. rhodozyma. This species is the only fungus known to produce the economically relevant carotenoid astaxanthin. Although Phaffia was originally found in the Northern hemisphere, its [...] Read more.
Phaffia is an orange-colored basidiomycetous yeast genus of the order Cystofilobasidiales that contains a single species, P. rhodozyma. This species is the only fungus known to produce the economically relevant carotenoid astaxanthin. Although Phaffia was originally found in the Northern hemisphere, its diversity in the southern part of the globe has been shown to be much greater. Here we analyze the genomes of two Australasian lineages that are markedly distinct from P. rhodozyma. The two divergent lineages were investigated within a comprehensive phylogenomic study of representatives of the Cystofilobasidiales that supported the recognition of two novel Phaffia species, for which we propose the names of P. australis sp. nov. and P. tasmanica sp. nov. Comparative genomics and other analyses confirmed that the two new species have the typical Phaffia hallmark—the six genes necessary for the biosynthesis of astaxanthin could be retrieved from the draft genome sequences, and this carotenoid was detected in culture extracts. In addition, the organization of the mating-type (MAT) loci is similar to that of P. rhodozyma, with synteny throughout most regions. Moreover, cases of trans-specific polymorphism involving pheromone receptor genes and pheromone precursor proteins in the three Phaffia species, together with their shared homothallism, provide additional support for their classification in a single genus. Full article
(This article belongs to the Section Molecular Microbiology and Immunology)
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24 pages, 3660 KiB  
Article
Two- and Three-Dimensional Tracking of MFA2 mRNA Molecules in Mating Yeast
by Polina Geva, Konstantin Komoshvili and Stella Liberman-Aronov
Cells 2020, 9(10), 2151; https://doi.org/10.3390/cells9102151 - 23 Sep 2020
Cited by 1 | Viewed by 3749
Abstract
Intracellular mRNA transport contributes to the spatio-temporal regulation of mRNA function and localized translation. In the budding yeast, Saccharomyces cerevisiae, asymmetric mRNA transport localizes ~30 specific mRNAs including those encoding polarity and secretion factors, to the bud tip. The underlying process involves [...] Read more.
Intracellular mRNA transport contributes to the spatio-temporal regulation of mRNA function and localized translation. In the budding yeast, Saccharomyces cerevisiae, asymmetric mRNA transport localizes ~30 specific mRNAs including those encoding polarity and secretion factors, to the bud tip. The underlying process involves RNA-binding proteins (RBPs), molecular motors, processing bodies (PBs), and the actin cytoskeleton. Recently, pheromone a-factor expression in mating yeast was discovered to depend on proper localization of its mRNA, MFA2 mRNAs in conjunction with PBs cluster at the shmoo tip to form “mating bodies”, from which a-factor is locally expressed. The mechanism ensuring the correct targeting of mRNA to the shmoo tip is poorly understood. Here we analyzed the kinetics and trajectories of MFA2 mRNA transport in living, alpha-factor treated yeast. Two- (2D) and three-dimensional (3D) analyses allowed us to reconstruct the granule tracks and estimate granule velocities. Tracking analysis of single MFA2 mRNA granules, labeled using a fluorescent aptamer system, demonstrated three types movement: vibrational, oscillatory and translocational. The mRNA granule transport was complex; a granule could change its movement behavior and composition during its journey to the shmoo. Processing body assembly and the actin-based motor, Myo4p, were involved in movement of MFA2 mRNA to the shmoo, but neither was required, indicating that multiple mechanisms for translocation were at play. Our visualization studies present a dynamic view of the localization mechanism in shmoo-bearing cells. Full article
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