scholarly journals The dopamine receptor D5 gene shows signs of independent erosion in toothed and baleen whales

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7758 ◽  
Author(s):  
Luís Q. Alves ◽  
Juliana Alves ◽  
Rodrigo Ribeiro ◽  
Raquel Ruivo ◽  
Filipe Castro
Keyword(s):  
Genetic Basis ◽  
Baleen Whales ◽  
Deep Diving ◽  
Dopaminergic Systems ◽  
High Affinity Receptor ◽  
Mammalian Genomes ◽  
Golden Mole ◽  
Phylogenetic Framework ◽  
Affinity Receptor ◽  
G Protein Coupled

To compare gene loci considering a phylogenetic framework is a promising approach to uncover the genetic basis of human diseases. Imbalance of dopaminergic systems is suspected to underlie some emerging neurological disorders. The physiological functions of dopamine are transduced via G-protein-coupled receptors, including DRD5 which displays a relatively higher affinity toward dopamine. Importantly, DRD5 knockout mice are hypertense, a condition emerging from an increase in sympathetic tone. We investigated the evolution of DRD5, a high affinity receptor for dopamine, in mammals. Surprisingly, among 124 investigated mammalian genomes, we found that Cetacea lineages (Mysticeti and Odontoceti) have independently lost this gene, as well as the burrowing Chrysochloris asiatica (Cape golden mole). We suggest that DRD5 inactivation parallels hypoxia-induced adaptations, such as peripheral vasoconstriction required for deep-diving in Cetacea, in accordance with the convergent evolution of vasoconstrictor genes in hypoxia-exposed animals. Our findings indicate that Cetacea are natural knockouts for DRD5 and might offer valuable insights into the mechanisms of some forms of vasoconstriction responses and hypertension in humans.

scholarly journals The dopamine receptor D5 gene shows signs of independent erosion in Toothed and Baleen whales

2019 ◽  
Author(s):  
Luís Q. Alves ◽  
Juliana Alves ◽  
Rodrigo Ribeiro ◽  
Raquel Ruivo ◽  
L. Filipe C. Castro
Keyword(s):  
Genetic Basis ◽  
Baleen Whales ◽  
Deep Diving ◽  
Dopaminergic Systems ◽  
High Affinity Receptor ◽  
Mammalian Genomes ◽  
Golden Mole ◽  
Phylogenetic Framework ◽  
Affinity Receptor ◽  
G Protein Coupled

AbstractTo compare gene loci considering a phylogenetic framework is a promising approach to uncover the genetic basis of human diseases. Imbalance of dopaminergic systems is suspected to underlie some emerging neurological disorders. The physiological functions of dopamine are transduced via G-protein-coupled receptors, including DRD5 which displays a relatively higher affinity towards dopamine. Importantly, DRD5 knockout mice are hypertense, a condition emerging from an increase in sympathetic tone. We investigated the evolution of DRD5, a high affinity receptor for dopamine, in mammals. Surprisingly, among 124 investigated mammalian genomes, we found that Cetacea lineages (Mysticeti and Odontoceti) have independently lost this gene, as well as the burrowing Chrysochloris asiatica (Cape golden mole). We suggest that DRD5 inactivation parallels hypoxia-induced adaptations, such as peripheral vasoconstriction required for deep-diving in Cetacea, in accordance with the convergent evolution of vasoconstrictor genes in hypoxia-exposed animals. Our findings indicate that Cetacea are natural knockouts for DRD5 and might offer valuable insights into the mechanisms of some forms of vasoconstriction responses and hypertension in humans.

scholarly journals Structural Basis of Arrestin Selectivity for Active Phosphorylated G Protein-Coupled Receptors

2021 ◽  
Vol 22 (22) ◽  
pp. 12481
Author(s):  
Preethi C. Karnam ◽  
Sergey A. Vishnivetskiy ◽  
Vsevolod V. Gurevich
Keyword(s):  
G Protein ◽  
Receptor Binding ◽  
G Protein Coupled Receptors ◽  
Structural Basis ◽  
Preferential Binding ◽  
High Affinity Receptor ◽  
Functional Forms ◽  
Affinity Receptor ◽  
G Protein Coupled ◽  
Receptor Conformation

Arrestins are a small family of proteins that bind G protein-coupled receptors (GPCRs). Arrestin binds to active phosphorylated GPCRs with higher affinity than to all other functional forms of the receptor, including inactive phosphorylated and active unphosphorylated. The selectivity of arrestins suggests that they must have two sensors, which detect receptor-attached phosphates and the active receptor conformation independently. Simultaneous engagement of both sensors enables arrestin transition into a high-affinity receptor-binding state. This transition involves a global conformational rearrangement that brings additional elements of the arrestin molecule, including the middle loop, in contact with a GPCR, thereby stabilizing the complex. Here, we review structural and mutagenesis data that identify these two sensors and additional receptor-binding elements within the arrestin molecule. While most data were obtained with the arrestin-1-rhodopsin pair, the evidence suggests that all arrestins use similar mechanisms to achieve preferential binding to active phosphorylated GPCRs.

scholarly journals Hydroxyeicosanoids Bind to and Activate the Low Affinity Leukotriene B4Receptor, BLT2

2001 ◽  
Vol 276 (15) ◽  
pp. 12454-12459 ◽  
Author(s):  
Takehiko Yokomizo ◽  
Kazuhiko Kato ◽  
Hiroshi Hagiya ◽  
Takashi Izumi ◽  
Takao Shimizu
Keyword(s):  
Inflammatory Diseases ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Ligand Specificity ◽  
Hydroxyeicosatetraenoic Acid ◽  
Ovary Cells ◽  
High Affinity Receptor ◽  
Arachidonate Metabolite ◽  
Affinity Receptor ◽  
G Protein Coupled

Leukotriene B4, an arachidonate metabolite, is a potent chemoattractant of leukocytes involved in various inflammatory diseases. Two G-protein-coupled receptors for leukotriene B4have been cloned and characterized. BLT1 (Yokomizo, T., Izumi, T., Chang, K., Takuwa, Y., and Shimizu, T. (1997)Nature387, 620–624) is a high affinity receptor exclusively expressed in leukocytes, and BLT2 (Yokomizo, T., Kato, K., Terawaki, K., Izumi, T., and Shimizu, T. (2000)J. Exp. Med.192, 421–432) is a low affinity receptor expressed more ubiquitously. Here we report the binding profiles of various BLT antagonists and eicosanoids to either BLT1 or BLT2 using the membrane fractions of Chinese hamster ovary cells stably expressing the receptor. BLT antagonists are grouped into three classes: BLT1-specific U-75302, BLT2-specific LY255283, and BLT1/BLT2 dual-specific ZK 158252 and CP 195543. We also show that 12(S)-hydroxyeicosatetraenoic acid, 12(S)-hydroperxyeicosatetraenoic acid, and 15(S)-hydroxyeicosatetraenoic acid competed with [3H]LTB4binding to BLT2, but not BLT1, dose dependently. These eicosanoids also cause calcium mobilization and chemotaxis through BLT2, again in contrast to BLT1. These findings suggest that BLT2 functions as a low affinity receptor, with broader ligand specificity for various eicosanoids, and mediates distinct biological and pathophysiological roles from BLT1.

scholarly journals IL-33 and Superantigenic Activation of Human Lung Mast Cells Induce the Release of Angiogenic and Lymphangiogenic Factors

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 145
Author(s):  
Leonardo Cristinziano ◽  
Remo Poto ◽  
Gjada Criscuolo ◽  
Anne Lise Ferrara ◽  
Maria Rosaria Galdiero ◽  
...  
Keyword(s):  
Mast Cells ◽  
Human Lung ◽  
Protein A ◽  
Protein L ◽  
Variable Regions ◽  
Prolonged Incubation ◽  
High Affinity ◽  
High Affinity Receptor ◽  
Affinity Receptor ◽  
Pleiotropic Functions

Human lung mast cells (HLMCs) express the high-affinity receptor FcεRI for IgE and are strategically located in different compartments of human lung, where they play a role in several inflammatory disorders and cancer. Immunoglobulin superantigens (e.g., protein A of Staphylococcus aureus and protein L of Peptostreptococcus magnus) bind to the variable regions of either the heavy (VH3) or light chain (κ) of IgE. IL-33 is a cytokine expressed by epithelial cells that exerts pleiotropic functions in the lung. The present study investigated whether immunoglobulin superantigens protein A and protein L and IL-33 caused the release of inflammatory (histamine), angiogenic (VEGF-A) and lymphangiogenic (VEGF-C) factors from HLMCs. The results show that protein A and protein L induced the rapid (30 min) release of preformed histamine from HLMCs. By contrast, IL-33 did not induce the release of histamine from lung mast cells. Prolonged incubation (12 h) of HLMCs with superantigens and IL-33 induced the release of VEGF-A and VEGF-C. Preincubation with IL-33 potentiated the superantigenic release of histamine, angiogenic and lymphangiogenic factors from HLMCs. Our results suggest that IL-33 might enhance the inflammatory, angiogenic and lymphangiogenic activities of lung mast cells in pulmonary disorders.

The Temporal Distribution of the 1α,25-Dihydroxycholecalciferol Receptor in the Rat Jejunal Villus

1984 ◽  
Vol 67 (3) ◽  
pp. 285-290 ◽  
Author(s):  
S. D. H. Chan ◽  
D. Atkins
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Calcium Absorption ◽  
Sedimentation Coefficient ◽  
Temporal Distribution ◽  
High Affinity ◽  
High Affinity Receptor ◽  
Affinity Receptor ◽  
Cell Fractions ◽  
Crypt Cells

1. The distribution of the 1α,25-dihydroxycholecalciferol receptor was studied in enterocytes isolated from the upper, mid and lower villus and crypt cells of the jejunum of normal and rachitic rats. 2. In all cell fractions a high-affinity receptor (KD ⋍ 0.07 nmol/l) with a sedimentation coefficient of 3.5S was demonstrated. 3. In normal rats there was a 60% reduction in receptor numbers in crypt cells compared with the mid and upper villous cells. 4. Vitamin D deficiency led to a reduction in receptor numbers in all cell fractions (45% upper villus, 78% crypt cells). 5. The data are compatible with the concept of calcium absorption occurring in the differentiated villous cells and also account for the reduction in absorption in rachitic animals.

scholarly journals Palmitoylation of Cytoskeleton Associated Protein 4 by DHHC2 Regulates Antiproliferative Factor-mediated Signaling

2009 ◽  
Vol 20 (5) ◽  
pp. 1454-1463 ◽  
Author(s):  
Sonia L. Planey ◽  
Susan K. Keay ◽  
Chen-Ou Zhang ◽  
David A. Zacharias
Keyword(s):  
Epithelial Cells ◽  
Cellular Proliferation ◽  
Phosphorylated Protein ◽  
Normal Bladder ◽  
High Affinity Receptor ◽  
Palmitoyl Acyltransferase ◽  
Cellular Behaviors ◽  
Affinity Receptor ◽  
Induced Changes

Previously, we identified cytoskeleton-associated protein 4 (CKAP4) as a major substrate of the palmitoyl acyltransferase, DHHC2, using a novel proteomic method called palmitoyl-cysteine identification, capture and analysis (PICA). CKAP4 is a reversibly palmitoylated and phosphorylated protein that links the ER to the cytoskeleton. It is also a high-affinity receptor for antiproliferative factor (APF), a small sialoglycopeptide secreted from bladder epithelial cells of patients with interstitial cystitis (IC). The role of DHHC2-mediated palmitoylation of CKAP4 in the antiproliferative response of HeLa and normal bladder epithelial cells to APF was investigated. Our data show that siRNA-mediated knockdown of DHHC2 and consequent suppression of CKAP4 palmitoylation inhibited the ability of APF to regulate cellular proliferation and blocked APF-induced changes in the expression of E-cadherin, vimentin, and ZO-1 (genes known to play a role in cellular proliferation and tumorigenesis). Immunocytochemistry revealed that CKAP4 palmitoylation by DHHC2 is required for its trafficking from the ER to the plasma membrane and for its nuclear localization. These data suggest an important role for DHHC2-mediated palmitoylation of CKAP4 in IC and in opposing cancer-related cellular behaviors and support the idea that DHHC2 is a tumor suppressor.

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