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The Adhesion GPCR GPR125 is specifically expressed in the choroid plexus and is upregulated following brain injury.

Pickering C, Hägglund M, Szmydynger-Chodobska J, Marques F, Palha JA, Waller L, Chodobski A, Fredriksson R, Lagerström MC, Schiöth HB - BMC Neurosci (2008)

Bottom Line: A single copy of GPR125 was found in many vertebrate genomes.Induction of inflammation by LPS did not change GPR125 expression.However, GPR125 expression was transiently increased (almost 2-fold) at 4 h after traumatic brain injury (TBI) followed by a decrease (approximately 4-fold) from 2 days onwards in the choroid plexus as well as increased expression (2-fold) in the hippocampus that was delayed until 1 day after injury.

View Article: PubMed Central - HTML - PubMed

Affiliation: Uppsala University, Department of Neuroscience, Functional Pharmacology, BMC, Box 593, SE-75124, Uppsala, Sweden. chris.pickering@neuro.uu.se

ABSTRACT

Background: GPR125 belongs to the family of Adhesion G protein-coupled receptors (GPCRs). A single copy of GPR125 was found in many vertebrate genomes. We also identified a Drosophila sequence, DmCG15744, which shares a common ancestor with the entire Group III of Adhesion GPCRs, and also contains Ig, LRR and HBD domains which were observed in mammalian GPR125.

Results: We found specific expression of GPR125 in cells of the choroid plexus using in situ hybridization and protein-specific antibodies and combined in situ/immunohistochemistry co-localization using cytokeratin, a marker specific for epithelial cells. Induction of inflammation by LPS did not change GPR125 expression. However, GPR125 expression was transiently increased (almost 2-fold) at 4 h after traumatic brain injury (TBI) followed by a decrease (approximately 4-fold) from 2 days onwards in the choroid plexus as well as increased expression (2-fold) in the hippocampus that was delayed until 1 day after injury.

Conclusion: These findings suggest that GPR125 plays a functional role in choroidal and hippocampal response to injury.

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Related in: MedlinePlus

A) A consensus neighbour-joining tree calculated in protdist and neighbour from the Phylip package version 3.66 with default settings and 1000 replicates. Methuselah-like/Drosophila and Secretin/B1 sequences were downloaded from (Harmar, 2001). The Adhesion group has been named III according to Bjarnadottir and colleagues (Bjarnadottir et al., 2004) and is indicated by the shaded circle. B) Representation of Adhesion Group III N-terminals and their incorporated domains identified via rps-blast at  with a cutoff value of 0.1. The sequences are grouped according to Bjarnadottir and colleagues division in group I-VIII. Represented sequences are H – Homo sapiens, Tn – Tetraodon nigroviridis, Tr – Takifugu rubripes and Dm – Drosophila melanogaster. Possible domains are GPS – GPCR proteolytic site, HBD – hormone binding domain, LRR – leucine rich repeats, Ig – immunoglobulin and 7TM – seven transmembrane domains. The numbers above the N-terminal indicate the length in number of amino acids.
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Figure 1: A) A consensus neighbour-joining tree calculated in protdist and neighbour from the Phylip package version 3.66 with default settings and 1000 replicates. Methuselah-like/Drosophila and Secretin/B1 sequences were downloaded from (Harmar, 2001). The Adhesion group has been named III according to Bjarnadottir and colleagues (Bjarnadottir et al., 2004) and is indicated by the shaded circle. B) Representation of Adhesion Group III N-terminals and their incorporated domains identified via rps-blast at with a cutoff value of 0.1. The sequences are grouped according to Bjarnadottir and colleagues division in group I-VIII. Represented sequences are H – Homo sapiens, Tn – Tetraodon nigroviridis, Tr – Takifugu rubripes and Dm – Drosophila melanogaster. Possible domains are GPS – GPCR proteolytic site, HBD – hormone binding domain, LRR – leucine rich repeats, Ig – immunoglobulin and 7TM – seven transmembrane domains. The numbers above the N-terminal indicate the length in number of amino acids.

Mentions: A phylogenetic tree was prepared using the Adhesion, Secretin, and Methuselah families (Figure 1A). GPR123, GPR124 and GPR125 grouped together (shaded grey in Figure 1A) and the Drosophila receptor DmCG15744 branches before the cluster of these three receptors. Domains were identified through the conserved domain database (rps-blast) and the N-terminal regions with each domain are illustrated in Figure 1B. The GPCR proteolytic site (GPS) domain is conserved in all sequences except DmCG15744. Rodent GPR125 have longer N-terminal regions than human GPR125 but all contain hormone binding domains (HBD), immunoglobulin (Ig) and leucine-rich-repeat (LRR) domains. In contrast, teleosts either have an HBD and Ig domain (Takifugu rubripes) or Ig and LRR domain (Tetraodon nigroviridis) but not all three. DmCG15744, however, contained all three domains and was therefore consistent with rodent GPR125. An analysis of the conservation of intron-exon boundaries is provided in Additional file 1. Intron-exon boundaries were conserved between human, rat and mouse GPR125 and between the two teleost sequences but there was no conservation of boundaries between these and DmCG15744.


The Adhesion GPCR GPR125 is specifically expressed in the choroid plexus and is upregulated following brain injury.

Pickering C, Hägglund M, Szmydynger-Chodobska J, Marques F, Palha JA, Waller L, Chodobski A, Fredriksson R, Lagerström MC, Schiöth HB - BMC Neurosci (2008)

A) A consensus neighbour-joining tree calculated in protdist and neighbour from the Phylip package version 3.66 with default settings and 1000 replicates. Methuselah-like/Drosophila and Secretin/B1 sequences were downloaded from (Harmar, 2001). The Adhesion group has been named III according to Bjarnadottir and colleagues (Bjarnadottir et al., 2004) and is indicated by the shaded circle. B) Representation of Adhesion Group III N-terminals and their incorporated domains identified via rps-blast at  with a cutoff value of 0.1. The sequences are grouped according to Bjarnadottir and colleagues division in group I-VIII. Represented sequences are H – Homo sapiens, Tn – Tetraodon nigroviridis, Tr – Takifugu rubripes and Dm – Drosophila melanogaster. Possible domains are GPS – GPCR proteolytic site, HBD – hormone binding domain, LRR – leucine rich repeats, Ig – immunoglobulin and 7TM – seven transmembrane domains. The numbers above the N-terminal indicate the length in number of amino acids.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2571103&req=5

Figure 1: A) A consensus neighbour-joining tree calculated in protdist and neighbour from the Phylip package version 3.66 with default settings and 1000 replicates. Methuselah-like/Drosophila and Secretin/B1 sequences were downloaded from (Harmar, 2001). The Adhesion group has been named III according to Bjarnadottir and colleagues (Bjarnadottir et al., 2004) and is indicated by the shaded circle. B) Representation of Adhesion Group III N-terminals and their incorporated domains identified via rps-blast at with a cutoff value of 0.1. The sequences are grouped according to Bjarnadottir and colleagues division in group I-VIII. Represented sequences are H – Homo sapiens, Tn – Tetraodon nigroviridis, Tr – Takifugu rubripes and Dm – Drosophila melanogaster. Possible domains are GPS – GPCR proteolytic site, HBD – hormone binding domain, LRR – leucine rich repeats, Ig – immunoglobulin and 7TM – seven transmembrane domains. The numbers above the N-terminal indicate the length in number of amino acids.
Mentions: A phylogenetic tree was prepared using the Adhesion, Secretin, and Methuselah families (Figure 1A). GPR123, GPR124 and GPR125 grouped together (shaded grey in Figure 1A) and the Drosophila receptor DmCG15744 branches before the cluster of these three receptors. Domains were identified through the conserved domain database (rps-blast) and the N-terminal regions with each domain are illustrated in Figure 1B. The GPCR proteolytic site (GPS) domain is conserved in all sequences except DmCG15744. Rodent GPR125 have longer N-terminal regions than human GPR125 but all contain hormone binding domains (HBD), immunoglobulin (Ig) and leucine-rich-repeat (LRR) domains. In contrast, teleosts either have an HBD and Ig domain (Takifugu rubripes) or Ig and LRR domain (Tetraodon nigroviridis) but not all three. DmCG15744, however, contained all three domains and was therefore consistent with rodent GPR125. An analysis of the conservation of intron-exon boundaries is provided in Additional file 1. Intron-exon boundaries were conserved between human, rat and mouse GPR125 and between the two teleost sequences but there was no conservation of boundaries between these and DmCG15744.

Bottom Line: A single copy of GPR125 was found in many vertebrate genomes.Induction of inflammation by LPS did not change GPR125 expression.However, GPR125 expression was transiently increased (almost 2-fold) at 4 h after traumatic brain injury (TBI) followed by a decrease (approximately 4-fold) from 2 days onwards in the choroid plexus as well as increased expression (2-fold) in the hippocampus that was delayed until 1 day after injury.

View Article: PubMed Central - HTML - PubMed

Affiliation: Uppsala University, Department of Neuroscience, Functional Pharmacology, BMC, Box 593, SE-75124, Uppsala, Sweden. chris.pickering@neuro.uu.se

ABSTRACT

Background: GPR125 belongs to the family of Adhesion G protein-coupled receptors (GPCRs). A single copy of GPR125 was found in many vertebrate genomes. We also identified a Drosophila sequence, DmCG15744, which shares a common ancestor with the entire Group III of Adhesion GPCRs, and also contains Ig, LRR and HBD domains which were observed in mammalian GPR125.

Results: We found specific expression of GPR125 in cells of the choroid plexus using in situ hybridization and protein-specific antibodies and combined in situ/immunohistochemistry co-localization using cytokeratin, a marker specific for epithelial cells. Induction of inflammation by LPS did not change GPR125 expression. However, GPR125 expression was transiently increased (almost 2-fold) at 4 h after traumatic brain injury (TBI) followed by a decrease (approximately 4-fold) from 2 days onwards in the choroid plexus as well as increased expression (2-fold) in the hippocampus that was delayed until 1 day after injury.

Conclusion: These findings suggest that GPR125 plays a functional role in choroidal and hippocampal response to injury.

Show MeSH
Related in: MedlinePlus