Oligomerization of G-Protein-Coupled Receptors: Lessons from the Yeast<i>Saccharomyces cerevisiae</i>

Overton, Mark C.; Chinault, Sharon L.; Blumer, Kendall J.

doi:10.1128/ec.4.12.1963-1970.2005

Cited by 46 publications

(34 citation statements)

References 115 publications

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“…The knockout of a single receptor in S. macrospora has no obvious effect on fruiting body development and indicates that one receptor can compensate for the loss of the other receptor (Mayrhofer et al 2006). This is supported by a growing body of evidence suggesting that G protein-coupled receptors exist as homo-or heterooligomers (Bulenger et al 2005;Overton et al 2005). Overton et al (2005) propose in a model that oligomerized receptors can activate a single G protein heterotrimer or alternatively each receptor monomer activates individual G proteins.…”

Section: Discussionmentioning

confidence: 60%

“…This is supported by a growing body of evidence suggesting that G protein-coupled receptors exist as homo-or heterooligomers (Bulenger et al 2005;Overton et al 2005). Overton et al (2005) propose in a model that oligomerized receptors can activate a single G protein heterotrimer or alternatively each receptor monomer activates individual G proteins.…”

Section: Discussionmentioning

confidence: 72%

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Three α-Subunits of Heterotrimeric G Proteins and an Adenylyl Cyclase Have Distinct Roles in Fruiting Body Development in the Homothallic Fungus Sordaria macrospora

et al. 2008

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Sordaria macrospora, a self-fertile filamentous ascomycete, carries genes encoding three different a-subunits of heterotrimeric G proteins (gsa, G protein Sordaria alpha subunit). We generated knockout strains for all three gsa genes (Dgsa1, Dgsa2, and Dgsa3) as well as all combinations of double mutants. Phenotypic analysis of single and double mutants showed that the genes for Ga-subunits have distinct roles in the sexual life cycle. While single mutants show some reduction of fertility, double mutants Dgsa1Dgsa2 and Dgsa1Dgsa3 are completely sterile. To test whether the pheromone receptors PRE1 and PRE2 mediate signaling via distinct Ga-subunits, two recently generated Dpre strains were crossed with all Dgsa strains. Analyses of the corresponding double mutants revealed that compared to GSA2, GSA1 is a more predominant regulator of a signal transduction cascade downstream of the pheromone receptors and that GSA3 is involved in another signaling pathway that also contributes to fruiting body development and fertility. We further isolated the gene encoding adenylyl cyclase (AC) (sac1) for construction of a knockout strain. Analyses of the three DgsaDsac1 double mutants and one Dgsa2Dgsa3Dsac1 triple mutant indicate that SAC1 acts downstream of GSA3, parallel to a GSA1-GSA2-mediated signaling pathway. In addition, the function of STE12 and PRO41, two presumptive signaling components, was investigated in diverse double mutants lacking those developmental genes in combination with the gsa genes. This analysis was further completed by expression studies of the ste12 and pro41 transcripts in wild-type and mutant strains. From the sum of all our data, we propose a model for how different Ga-subunits interact with pheromone receptors, adenylyl cyclase, and STE12 and thus cooperatively regulate sexual development in S. macrospora.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 72%

Three α-Subunits of Heterotrimeric G Proteins and an Adenylyl Cyclase Have Distinct Roles in Fruiting Body Development in the Homothallic Fungus Sordaria macrospora

et al. 2008

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“…A similar mechanism was proposed to mediate the function of membrane receptors, where GXXXG-like motifs were found to be present in transmembrane domains of many G proteincoupled receptors. These include the ␣-factor receptor of various yeast species, class A amine and cannabinoid receptors, class B secretin-like receptors, and class C metabotropic receptors (28). Mutation within the GXXXG motif was shown to reduce expression and increase receptor retention in intracellular compartments such as the endoplasmic reticulum.…”

Section: Discussionmentioning

confidence: 99%

Identification of the amino acid sequence that targets peroxiredoxin 6 to lysosome-like structures of lung epithelial cells

Sorokina

Feinstein

Milovanova

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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Peroxiredoxin 6 (Prdx6), an enzyme with glutathione peroxidase and PLA2 (aiPLA2) activities, is highly expressed in respiratory epithelium, where it participates in phospholipid turnover and antioxidant defense. Prdx6 has been localized by immunocytochemistry and subcellular fractionation to acidic organelles (lung lamellar bodies and lysosomes) and cytosol. On the basis of their pH optima, we have postulated that protein subcellular localization determines the balance between the two activities of Prdx6. Using green fluorescent protein-labeled protein expression in alveolar epithelial cell lines, we showed Prdx6 localization to organellar structures resembling lamellar bodies in mouse lung epithelial (MLE-12) cells and lysosomes in A549 cells. Localization within lamellar bodies/lysosomes was in the luminal compartment. Targeting to lysosome-like organelles was abolished by the deletion of amino acids 31-40 from the Prdx6 NH2-terminal region; deletion of the COOH-terminal region had no effect. A green fluorescent protein-labeled peptide containing only amino acids 31-40 showed lysosomal targeting that was abolished by mutation of S32 or G34 within the peptide. Studies with mutated protein indicated that lipid binding was not necessary for Prdx6 targeting. This peptide sequence has no homology to known organellar targeting motifs. These studies indicate that the localization of Prdx6 in acidic organelles and consequent PLA2 activity depend on a novel 10-aa peptide located at positions 31-40 of the protein.

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“…Gpa2 associates with the plasma membrane via post-translational palmitoylation and myristoylation (Dohlman et al, 2001; Overton et al, 2005). Gpa2 activates both cAMP-dependent and cAMP-independent pathways of PKA activation.…”

Section: Pka and Carbon-source Sensing Pathwaysmentioning

confidence: 99%

Less is more: Nutrient limitation induces cross-talk of nutrient sensing pathways with NAD+ homeostasis and contributes to longevity

Tsang

Lin

2015

Front. Biol.

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Nutrient sensing pathways and their regulation grant cells control over their metabolism and growth in response to changing nutrients. Factors that regulate nutrient sensing can also modulate longevity. Reduced activity of nutrient sensing pathways such as glucose-sensing PKA, nitrogen-sensing TOR and S6 kinase homolog Sch9 have been linked to increased life span in the yeast, Saccharomyces cerevisiae, and higher eukaryotes. Recently, reduced activity of amino acid sensing SPS pathway was also shown to increase yeast life span. Life span extension by reduced SPS activity requires enhanced NAD+ (nicotinamide adenine dinucleotide, oxidized form) and nicotinamide riboside (NR, a NAD+ precursor) homeostasis. Maintaining adequate NAD+ pools has been shown to play key roles in life span extension, but factors regulating NAD+ metabolism and homeostasis are not completely understood. Recently, NAD+ metabolism was also linked to the phosphate (Pi)-sensing PHO pathway in yeast. Canonical PHO activation requires Pi-starvation. Interestingly, NAD+ depletion without Pi-starvation was sufficient to induce PHO activation, increasing NR production and mobilization. Moreover, SPS signaling appears to function in parallel with PHO signaling components to regulate NR/NAD+ homeostasis. These studies suggest that NAD+ metabolism is likely controlled by and/or coordinated with multiple nutrient sensing pathways. Indeed, cross-regulation of PHO, PKA, TOR and Sch9 pathways was reported to potentially affect NAD+ metabolism; though detailed mechanisms remain unclear. This review discusses yeast longevity-related nutrient sensing pathways and possible mechanisms of life span extension, regulation of NAD+ homeostasis, and cross-talk among nutrient sensing pathways and NAD+ homeostasis.

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Oligomerization of G-Protein-Coupled Receptors: Lessons from the YeastSaccharomyces cerevisiae

Cited by 46 publications

References 115 publications

Three α-Subunits of Heterotrimeric G Proteins and an Adenylyl Cyclase Have Distinct Roles in Fruiting Body Development in the Homothallic Fungus Sordaria macrospora

Three α-Subunits of Heterotrimeric G Proteins and an Adenylyl Cyclase Have Distinct Roles in Fruiting Body Development in the Homothallic Fungus Sordaria macrospora

Identification of the amino acid sequence that targets peroxiredoxin 6 to lysosome-like structures of lung epithelial cells

Less is more: Nutrient limitation induces cross-talk of nutrient sensing pathways with NAD+ homeostasis and contributes to longevity

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