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Fourteen novel human members of mitochondrial solute carrier family 25 (SLC25) widely expressed in the central nervous system
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. (Farmakologi 3)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. (Farmakologi 3)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. (Farmakologi 3)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. (Farmakologi 3)
2006 (English)In: Genomics, ISSN 0888-7543, E-ISSN 1089-8646, Vol. 88, no 6, 779-790 p.Article in journal (Refereed) Published
Abstract [en]

Members of the solute carrier family 25 (SLC25) are known to transport molecules over the mitochondrial membrane. In this paper we present 14 novel members of SLC25 family in human. These were provided with following gene symbols by the HGNC: SLC25A32, SLC25A33, SLC25A34. SLC25A35, SLC25A37, SLC25A38, SLC25A39, SLC25A40, SLC25A41, SLC25A42, SLC25A43, SLC25A44, SLC25A45, and SLC25A46. We also identified the orthologues for these genes in rat and mouse. Moreover, we found yeast orthologues for 9 of these genes and show that the predicted substrate binding residues are highly conserved in the human and yeast proteins. We performed a comprehensive tissue localization study for 9 of these genes on a panel of 30 rat tissues with quantitative real-time polymerse chain reaction. We detected their mRNA in a wide number of tissues, both in brain and in periphery. This study provides an overall roadmap of the repertoire of the SLC25 family in mammals. showing that there are at least 46 genes in the human genome coding for mitochondrial transporters.

Place, publisher, year, edition, pages
2006. Vol. 88, no 6, 779-790 p.
Keyword [en]
Mitochondrial transporter, SLC, human, rat, mouse, expression
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-24980DOI: 10.1016/j.ygeno.2006.06.016ISI: 000242597500014PubMedID: 16949250OAI: oai:DiVA.org:uu-24980DiVA: diva2:52754
Available from: 2007-02-08 Created: 2007-02-08 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Function, Pharmacology, Evolution and Anatomical Localization of G Protein-Coupled Receptors and Solute Carriers
Open this publication in new window or tab >>Function, Pharmacology, Evolution and Anatomical Localization of G Protein-Coupled Receptors and Solute Carriers
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The G protein-coupled receptors (GPCRs) and solute carriers (SLC) are two large families of membrane-bound proteins. The aim of this study was to characterize these two families in terms of evolution and function. The melanocortin (MC) receptors belong to the Rhodopsin family of GPCRs and we cloned the MC4 and MC5 receptors from the rainbow trout, MC3 and MC5 from the spiny dogfish and MCa and MCb from the river lamprey. Pharmacological characterization of the cloned MC receptors demonstrated higher affinity for adrenocorticotropic hormone (ACTH) compared to melanocyte stimulating hormone (MSH) peptides (alpha-, beta- and gamma-MSH). We performed expression analysis with reverse transcription PCR, which showed that the MC4 and MC5 receptors in the rainbow trout are expressed centrally as well as in peripheral tissues. The dogfish MC3 and MC5 receptors were expressed in the brain, while the lamprey MCa and MCb receptors were expressed in the periphery. An extensive tissue localization analysis was performed for the entire family of Adhesion GPCRs in the rat and mouse. Using quantitative real-time PCR (qRT-PCR) we discovered that the majority of GPCRs were expressed either specifically in the CNS or ubiquitously in the CNS and peripheral tissues. We identified all non-olfactory GPCRs in the dog and classified them into Adhesion, Frizzled, Glutamate, Rhodopsin and Secretin families. The dog GPCR repertoire seemed to be more similar to the human repertoire than to the repertoires in rodents. Solute carrier family 25 includes mitochondrial membrane transporters. Using bioinformatics techniques we identified 14 novel members of the SLC25 family, which now has 46 members. We identified orthologs of the novel SLC25 family members in yeast and performed expression analysis of 9 of them with qRT-PCR on a panel containing 30 central and peripheral tissues from the rat. To conclude, this study has expanded our knowledge of the repertoire of genes coding for membrane-bound proteins and provided information about their functional roles.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 49 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 437
National Category
Pharmacology and Toxicology
Research subject
Medicine
Identifiers
urn:nbn:se:uu:diva-99413 (URN)978-91-554-7466-9 (ISBN)
Public defence
2009-04-24, Room B41, BMC, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2009-04-03 Created: 2009-03-13 Last updated: 2009-09-04Bibliographically approved

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Haitina, Tatjana

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