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Long evolutionary conservation and considerable tissue specificity of several atypical solute carrier transporters
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
2011 (English)In: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 478, no 1-2, 11-18 p.Article in journal (Refereed) Published
Abstract [en]

The superfamily of Solute Carriers (SLCs) has around 384 members in the human genome grouped into at least 48 families. While many of these transporters have been well characterized with established important biological functions, there are few recently identified genes that are not studied regarding tissue distribution or evolutionary origin. Here we study 14 of these recently discovered SLC genes (HIAT1, HIATL1, MFSD1, MFSD5, MFSD6, MFSD9, MFSD10, SLC7A14, SLC7A15, SLC10A6, SLC15A5, SLC16A12, SLC30A10 and SLC21A21) with the purpose to give much better picture over the sequence relationship and tissue expression of the diverse SLC gene family. We used a range of bioinformatic methods to classify each of these genes into the different SLC gene families. We found that 9 of the 14 atypical SLCs are distant members of the Major Facilitator Superfamily (MFS) clan while the others belong to the APC clan, the DMT clan, the CPA_AT clan and the IT clan. We found most of the genes to be highly evolutionary conserved, likely to be present in most bilateral species, except for SLC21A21 that we found only present in mammals. Several of these transporter genes have highly specific tissue expression profile while it is notable that most are expressed in the CNS with the exception of SLC21A21 and SLC15A5. This work provides fundamental information on 14 transporters that previously have not received much attention enabling a more comprehensive view over the SLC superfamily.

Place, publisher, year, edition, pages
2011. Vol. 478, no 1-2, 11-18 p.
Keyword [en]
APC, CNS, Kidney, Liver, MFS, Transport
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-135048DOI: 10.1016/j.gene.2010.10.011ISI: 000290888100002PubMedID: 21044875OAI: oai:DiVA.org:uu-135048DiVA: diva2:374311
Available from: 2010-12-03 Created: 2010-12-03 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Functional Characterization of Centrally Expressed Solute Carriers and G Protein-Coupled Receptors
Open this publication in new window or tab >>Functional Characterization of Centrally Expressed Solute Carriers and G Protein-Coupled Receptors
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Transmembrane proteins are gatekeepers of the cells; controlling the transport of substrates as well as communicating signals among cells and between the organelles and cytosol. Solute carriers (SLC) and G protein-coupled receptors (GPCR) are the largest family of membrane transporters and membrane receptors respectively. The overall aim of this thesis was to provide a basic understanding of some of the novel SLCs and GPCRs with emphasis on expression, transport property, evolution and probable function.

The first part of the thesis directs towards the study of some novel solute carriers. In an initial study, we provided an overall picture of the sequence relationship and tissue expression of 14 diverse atypical SLCs confirming some of their evolutionary conservation and highly specific expression pattern. The focus then was on the SLC17 family (mainly vesicular proteins) and a novel member named Slc17a9. This study revealed that SLC17 family could be divided into four main phylogenetic clades which were all present before the divergence of the insect lineage with Slc17a9 having the most restricted evolutionary history. Detailed expression study of Slc17a9 in the mouse brain suggests that it is also expressed in some regions important for purinergic neurotransmission. Further, we deorphanised an aminoacid transporter Slc38a7 which was expressed in a majority of neurons in the CNS and showed that it preferably mediate transport of L–glutamine and L–histidine.

The second part of the thesis focuses on the study of two GPCRs belonging to the Rhodopsin superfamily, Gpr162 and Gpr153. A phylogenetic analysis revealed that both Gpr153 and Gpr162 originated from a common ancestor before the radiation of the mammalian lineage. Expression study revealed that Gpr162 had a predominant expression in the CNS and relatively lower expression in the other tissue tested whereas Gpr153 had a more widespread and similar expression pattern in both CNS and peripheral tissues. The functional studies of the two GPCRs were done using the antisense oligodeoxynucleotide knockdown rat model. These studies provided evidence linking the orphan Gpr162 gene with the regulation of food intake– related behaviour whereas Gpr153 gene caused only a slight reduction in food intake.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 51 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 689
Keyword
GPCR, SLC, Gpr153, Gpr162, Slc17, Slc38
National Category
Neurosciences
Research subject
Neuroscience
Identifiers
urn:nbn:se:uu:diva-156832 (URN)978-91-554-8120-9 (ISBN)
Public defence
2011-09-22, B42, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2011-09-01 Created: 2011-08-09 Last updated: 2011-11-03Bibliographically approved

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