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The overall repertoire of G protein-coupled receptor in rats
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience, Pharmacology.
Manuscript (Other academic)
Identifiers
URN: urn:nbn:se:uu:diva-94265OAI: oai:DiVA.org:uu-94265DiVA: diva2:168055
Available from: 2006-04-07 Created: 2006-04-07 Last updated: 2010-01-13Bibliographically approved
In thesis
1. G Protein-Coupled Receptors; Discovery of New Human Members and Analyses of the Entire Repertoires in Human, Mouse and Rat
Open this publication in new window or tab >>G Protein-Coupled Receptors; Discovery of New Human Members and Analyses of the Entire Repertoires in Human, Mouse and Rat
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

G protein-coupled receptors (GPCRs) are signal mediators that have a prominent role in the regulation of physiological processes and they make up the targets for 30-45% of all drugs.

Papers I and II describe the discovery of new human GPCRs belonging to the Rhodopsin family, a family which contains many common drug targets. The new receptors have only weak relationships to previously known GPCRs. However, they have been evolutionary conserved in several species and most of them display distinct expression patterns.

In paper III we identified new human GPCRs belonging to the Adhesion family, which is characterised by very long N-termini containing conserved domains. The different compositions of conserved domains as well as the expression patterns suggest that the Adhesions can have several different functions.

In paper IV we revealed remarkable species variations in the repertoires of Trace Amine-Associated Receptors (TAARs), which are relatives of the biogenic amine receptors. The human, mouse and rat TAAR genes are located in only one locus and are therefore most likely the result of gene tandem duplications. 47 of the 57 zebrafish TAARs were mapped to nine different loci on six chromosomes containing from 1 to 27 genes each. This study suggests that the TAARs arose through several different mechanisms involving tetraploidisation, block duplications, and local duplication events.

Papers V and VI are overall analyses of the repertoires of GPCRs in humans, mice and rats; which contain approximately 800, 1800 and 1900 members, respectively. The repertoires were compared to distinguish between species-specific and common (orthologous) members, something which is important for example when predicting drug effects from experiments in rodents. The Glutamate, Adhesion, Frizzled and Secretin families show no or very little variation between human and rodents, whereas the repertoires of olfactory, vomeronasal and Taste2 receptors display large differences between all three species.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2006. 46 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 133
Keyword
Bioinformatics, G protein-coupled receptor, GPCR, Bioinformatics, Evolution, Orphan, Rhodopsin, Adhesion, Phylogeny, Bioinformatik
Identifiers
urn:nbn:se:uu:diva-6745 (URN)91-554-6522-6 (ISBN)
Public defence
2006-04-28, Room B21, BMC, Husargatan 3, Uppsala, 09:15
Opponent
Supervisors
Available from: 2006-04-07 Created: 2006-04-07 Last updated: 2011-06-17Bibliographically approved

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