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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

G protein-coupled receptors (GPCRs) are one of the largest families of proteins, and here we scan the recently sequenced chicken genome for GPCRs. We use a homology-based approach, utilizing comparisons with all human GPCRs, to detect and verify chicken GPCRs from translated genomic alignments and Genscan predictions. We present 557 manually curated sequences for GPCRs from the chicken genome, of which 455 were previously not annotated. More than 60% of the chicken Genscan gene predictions with a human ortholog needed curation, which drastically changed the average percentage identity between the human-chicken orthologous pairs (from 56.3% to 72.9%). Of the non-olfactory chicken GPCRs, 79% had a one-to-one orthologous relationship to a human GPCR. The Frizzled, Secretin, and subgroups of the Rhodopsin families have high proportions of orthologous pairs, although the percentage of amino acid identity varies. Other groups show large differences, such as the Adhesion family and GPCRs that bind exogenous ligands. The chicken has only three bitter Taste 2 receptors, and it also lacks an ortholog to human TAS1R2 (one of three GPCRs in the human genome in the Taste 1 receptor family [TAS1R]), implying that the chicken's ability and mode of detecting both bitter and sweet taste may differ from the human's. The chicken genome contains at least 229 olfactory receptors, and the majority of these (218) originate from a chicken-specific expansion. To our knowledge, this dataset of chicken GPCRs is the largest curated dataset from a single gene family from a non-mammalian vertebrate. Both the updated human GPCR dataset, as well the chicken GPCR dataset, are available for download.
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PMID:The G protein-coupled receptor subset of the chicken genome. 1674 57

Alternative splicing is an important mechanism to generate proteome diversity in higher eukaryotic organisms. We searched for splice variants of the human Adhesion family of G protein-coupled receptors (GPCRs) using mRNA sequences and expressed sequence tags. The results presented here describe 53 human splice variants among the 33 Adhesion GPCRs. Many of these variants appear to be coding for "functional" proteins (29) while the others are seemingly "non-functional" (24). Novel functional splice variants were found for: CD97, CELR3, EMR2, EMR3, GPR56, GPR110, GPR112-GPR114, GPR116, GPR123-GPR126, GPR133, HE6, and LEC1-LEC3. Splice variants for GPR116, GPR125, GPR126, and HE6 were found conserved in other species. Several of the functional splice variants lack one or more of the functional domains that are found in the N-termini of these receptors. These functional domains are likely to affect ligand binding or interaction with other proteins and these novel splice variants may have important roles for the specificity of interactions between these receptors and extracellular molecules. Another type of splice variants found here lacks a GPCR proteolytic site (GPS). The GPS domain has been shown to be essential for the proteolytic cleavage of the receptors N-termini and for cellular surface expression. We suggest that these alternative splice variants may be crucial for the function of the receptors while the seemingly non-functional splice variants may be a part of a regulative mechanism.
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PMID:Identification of novel splice variants of Adhesion G protein-coupled receptors. 1705 9

The Adhesion family of G protein-coupled receptors (GPCRs) includes 33 receptors and is the second largest GPCR family. Most of these proteins are still orphans and fairly little is known of their tissue distribution and evolutionary context. We report the evolutionary history of the Adhesion family protein GPR123 as well as mapping of GPR123 mRNA expression in mouse and rat using in situ hybridization and real-time PCR, respectively. GPR123 was found to be well conserved within the vertebrate lineage, especially within the transmembrane regions and in the distal part of the cytoplasmic tail, containing a potential PDZ binding domain. The real-time PCR data indicates that GPR123 is predominantly expressed in CNS. The in situ data show high expression in thalamic nuclei and regions containing large pyramidal cells like cortex layers 5 and 6 and subiculum. Moreover, we found distinct expression in amygdala, hypothalamus, inferior olive and spinal cord. The CNS specific expression, together with the high sequence conservation between the vertebrate sequences investigated, indicate that GPR123 may have an important role in the regulation of neuronal signal transduction.
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PMID:The evolutionary history and tissue mapping of GPR123: specific CNS expression pattern predominantly in thalamic nuclei and regions containing large pyramidal cells. 1721 99

The purpose of this article was to review recent progress in mining the gene repertoire and expressed sequence tags (ESTs) for the super-family of G protein-coupled receptors (GPCRs) in the form of a proceeding from the Nordic GPCR meeting held at the Nobel Forum, Karolinska Institute in August 2006. We update and give an overview of the expansion of the main families of GPCRs; Glutamate, Rhodopsin, Adhesion, Frizzled and Secretin (GRAFS) in perspective of fully sequenced genomes. We look into the most recent findings including the work that has been carried out on the spotted green puffer fish (Tetraodon nigroviridis), mouse (Mus musculus), chicken (Gallus gallus), slime mold (Dictyostelium discoideum) and the plant pathogenic fungus Magnaporthe grisea. We use examples from our recent work on chicken GPCRs to highlight the importance of detailed assembly and curation of sequences and how that can affect percentage similarity and phylogeny. ESTs can give valuable information about expression patterns. GPCRs have comparatively low numbers of EST suggesting that GPCRs are in generally expressed in lower amount than other genes. We discuss similarities in the evolution of the trace amine associated receptors with other sensory receptors.
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PMID:Mining the gene repertoire and ESTs for G protein-coupled receptors with evolutionary perspective. 1742 29

G protein-coupled receptors (GPCRs) are the largest family of membrane-bound receptors and also the targets of many drugs. Understanding of the functional significance of the wide structural diversity of GPCRs has been aided considerably in recent years by the sequencing of the human genome and by structural studies, and has important implications for the future therapeutic potential of targeting this receptor family. This article aims to provide a comprehensive overview of the five main human GPCR families--Rhodopsin, Secretin, Adhesion, Glutamate and Frizzled/Taste2--with a focus on gene repertoire, general ligand preference, common and unique structural features, and the potential for future drug discovery.
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PMID:Structural diversity of G protein-coupled receptors and significance for drug discovery. 1838 64

Insights into sequential leukocyte-endothelial interactions during leukocyte trafficking have been obtained through experiments using human umbilical vein endothelial cells (HUVEC) under flow conditions. To investigate leukocyte-brain endothelial cell interactions, we developed a dynamic in vitro system, using Transfected Human Brain Microvascular Endothelial Cells (THBMEC) and a parallel plate flow chamber. Human peripheral blood mononuclear cells (PBMC) were perfused across confluent THBMEC cultures at a velocity that approximates the rate found in human brain capillaries. Leukocyte-THBMEC interactions were visualized by phase-contrast microscopy, and images were captured on a CCD camera. To simulate inflammatory conditions, we activated THBMEC with the inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma), which up-regulated chemokine and adhesion molecule expression in THBMEC without affecting the distribution of immunoreactivity for tight junction-associated proteins. PBMC adhesion was enhanced by cytokine-mediated activation of THBMEC. G protein-coupled receptor (GPCR) activation was essential for leukocyte-THBMEC interaction, as pertussis toxin (PTX) treatment of PBMC abrogated PBMC adhesion to activated THBMEC. The anti-alpha4 integrin antibody, natalizumab, infused into MS patients, significantly reduced the adhesion of their ex vivo PBMC to activated THBMEC under flow conditions. Further study showed that alternatively spliced fibronectin containing the CS1 region (FN-CS1), but not Vascular Cell Adhesion Molecule type 1 (VCAM-1), was the ligand of alpha4 integrin on activated THBMEC. Blocking FN-CS1 abrogated PBMC adhesion on activated THBMEC, while anti-VCAM-1 antibodies had no effect. These results established a novel in vitro dynamic BBB model. We also demonstrated the dependence of leukocyte-endothelial interactions in this model on alpha4 integrins and FN-CS1.
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PMID:alpha4 Integrin/FN-CS1 mediated leukocyte adhesion to brain microvascular endothelial cells under flow conditions. 1934 24

Brain-specific angiogenesis inhibitor 2 (BAI2) is a member of adhesion-G protein-coupled receptors (GPCRs). BAI2 is dominantly expressed in the brain and its physiological ligands and functions are still unclear. Adhesion-GPCRs, including BAI2, commonly have a long N-terminal extracellular region (ECR) containing the GPCR proteolysis site (GPS) and the cleavage of the ECR at the GPS domain is suspected to be important for their function. In this study, we analyzed the proteolytic processing of BAI2 and its activation mechanism. Several cleaved C-terminal fragments of BAI2 were identified in mouse hippocampus. We confirmed that mutation in the GPS domain caused inhibition of the proteolysis of BAI2, which indicated the possibility that BAI2 was cleaved at the GPS domain. The association of the ECR putatively cleaved at the GPS domain and the C-terminal seven-transmembrane (7TM) fragment was detected by co-immunoprecipitation. We also found that furin prohormone convertase cleaved BAI2 at another site in the ECR. Additionally, the C-terminal fragment cleaved at the GPS domain specifically activated the nuclear factor of activated T-cells (NFAT) pathway. These results suggest that BAI2 is a functional GPCR regulated by proteolytic processing and activates the NFAT pathway.
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PMID:Brain-specific angiogenesis inhibitor 2 (BAI2) may be activated by proteolytic processing. 2036 54

Several families of G protein-coupled receptors (GPCRs) show no significant sequence similarities to each other, and it has been debated which of them share a common origin. We developed and performed integrated and independent HHsearch, Needleman--Wunsch-based and motif analyses on more than 6,600 unique GPCRs from 12 species. Moreover, we mined the evolutionary important Trichoplax adhaerens, Nematostella vectensis, Thalassiosira pseudonana, and Strongylocentrotus purpuratus genomes, revealing remarkably rich vertebrate-like GPCR repertoires already in the early Metazoan species. We found strong evidence that the Adhesion and Frizzled families are children to the cyclic AMP (cAMP) family with HHsearch homology probabilities of 99.8% and 99.4%, respectively, also supported by the Needleman--Wunsch analysis and several motifs. We also found that the large Rhodopsin family is likely a child of the cAMP family with an HHsearch homology probability of 99.4% and conserved motifs. Therefore, we suggest that the Adhesion and Frizzled families originated from the cAMP family in an event close to that which gave rise to the Rhodopsin family. We also found convincing evidence that the Rhodopsin family is parent to the important sensory families; Taste 2 and Vomeronasal type 1 as well as the Nematode chemoreceptor families. The insect odorant, gustatory, and Trehalose receptors, frequently referred to as GPCRs, form a separate cluster without relationship to the other families, and we propose, based on these and others' results, that these families are ligand-gated ion channels rather than GPCRs. Overall, we suggest common descent of at least 97% of the GPCRs sequences found in humans.
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PMID:Independent HHsearch, Needleman--Wunsch-based, and motif analyses reveal the overall hierarchy for most of the G protein-coupled receptor families. 2140 29

The Adhesion family is unique among the GPCR (G protein-coupled receptor) families because of several features including long N-termini with multiple domains. The gene repertoire has recently been mined in great detail in several species including mouse, rat, dog, chicken and the early vertebrate Branchiostoma (Branchiostoma floridae) and one of the most primitive animals, the cniderian Nematostella (Nematostella vectensis). There is a one-to-one relationship of the rodent (mouse and rat) and human orthologues with the exception the EMR2 and EMR3 that do not seem to have orthologues in either rat or mouse. All 33 human Adhesion GPCR genes are present in the dog genome but the dog genome also contains 5 additional full-length Adhesion genes. The dog and human Adhesion orthologues have higher average protein sequence identity than the rodent (rat and mouse) and the human sequences. The Adhesion family is well-represented in chicken with 21 one-to-one orthologous with humans, while 12 human Adhesion GPCRs lack a chicken ortholog. Branchiostoma has rich repertoire of Adhesion GPCRs with at least 37 genes. Moreover, the Adhesion GPCRs in Branchiostoma have several novel domains their N-termini, like Somatomedin B, Kringle, Lectin C-type, SRCR, LDLa, Immunoglobulin I-set, CUB and TNFR. Nematostella has also Adhesion GPCRs that are show domain structure and sequence similarities in the transmembrane regions with different classes of mammalian GPCRs. The Nematostella genome has a unique set of Adhesion-like sequences lacking GPS domains. There is considerable evidence showing that the Adhesion family is ancestral to the peptide hormone binding Secretin family of GPCRs.
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PMID:The adhesion GPCRs; gene repertoire, phylogeny and evolution. 2161 22

G protein-coupled receptors (GPCRs) in humans are classified into the five main families named Glutamate, Rhodopsin, Adhesion, Frizzled and Secretin according to the GRAFS classification. Previous results show that these mammalian GRAFS families are well represented in the Metazoan lineages, but they have not been shown to be present in Fungi. Here, we systematically mined 79 fungal genomes and provide the first evidence that four of the five main mammalian families of GPCRs, namely Rhodopsin, Adhesion, Glutamate and Frizzled, are present in Fungi and found 142 novel sequences between them. Significantly, we provide strong evidence that the Rhodopsin family emerged from the cAMP receptor family in an event close to the split of Opisthokonts and not in Placozoa, as earlier assumed. The Rhodopsin family then expanded greatly in Metazoans while the cAMP receptor family is found in 3 invertebrate species and lost in the vertebrates. We estimate that the Adhesion and Frizzled families evolved before the split of Unikonts from a common ancestor of all major eukaryotic lineages. Also, the study highlights that the fungal Adhesion receptors do not have N-terminal domains whereas the fungal Glutamate receptors have a broad repertoire of mammalian-like N-terminal domains. Further, mining of the close unicellular relatives of the Metazoan lineage, Salpingoeca rosetta and Capsaspora owczarzaki, obtained a rich group of both the Adhesion and Glutamate families, which in particular provided insight to the early emergence of the N-terminal domains of the Adhesion family. We identified 619 Fungi specific GPCRs across 79 genomes and revealed that Blastocladiomycota and Chytridiomycota phylum have Metazoan-like GPCRs rather than the GPCRs specific for Fungi. Overall, this study provides the first evidence of the presence of four of the five main GRAFS families in Fungi and clarifies the early evolutionary history of the GPCR superfamily.
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PMID:The origin of GPCRs: identification of mammalian like Rhodopsin, Adhesion, Glutamate and Frizzled GPCRs in fungi. 2223 61


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