title: Characterization of SLCO5A1/OATP5A1, a solute carrier transport protein with non-classical function.
abstract: Organic anion transporting polypeptides (OATP/SLCO) have been identified to mediate the uptake of a broad range of mainly amphipathic molecules. Human OATP5A1 was found to be expressed in the epithelium of many cancerous and non-cancerous tissues throughout the body but protein characterization and functional analysis have not yet been performed. This study focused on the biochemical characterization of OATP5A1 using Xenopus laevis oocytes and Flp-In T-REx-HeLa cells providing evidence regarding a possible OATP5A1 function. SLCO5A1 is highly expressed in mature dendritic cells compared to immature dendritic cells (∼6.5-fold) and SLCO5A1 expression correlates with the differentiation status of primary blood cells. A core- and complex- N-glycosylated polypeptide monomer of ∼105 kDa and ∼130 kDa could be localized in intracellular membranes and on the plasma membrane, respectively. Inducible expression of SLCO5A1 in HeLa cells led to an inhibitory effect of ∼20% after 96 h on cell proliferation. Gene expression profiling with these cells identified immunologically relevant genes (e.g. CCL20) and genes implicated in developmental processes (e.g. TGM2). A single nucleotide polymorphism leading to the exchange of amino acid 33 (L→F) revealed no differences regarding protein expression and function. In conclusion, we provide evidence that OATP5A1 might be a non-classical OATP family member which is involved in biological processes that require the reorganization of the cell shape, such as differentiation and migration.
authors.affiliation: Department of Dermatology and Allergology, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Sebastian
authors.affiliation: Institute of Pharmacology and Toxicology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Detro-Dassen
authors.affiliation: Institute of Biochemistry and Molecular Biology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.
authors.forename: Natalie
authors.initials: N
authors.lastname: Rinis
authors.affiliation: Institute of Biochemistry and Molecular Biology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Fahrenkamp
authors.affiliation: Institute of Biochemistry and Molecular Biology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Müller-Newen
authors.affiliation: Department of Dermatology and Allergology, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Hans F
authors.initials: HF
authors.lastname: Merk
authors.affiliation: Institute of Pharmacology and Toxicology, Medical Faculty of the RWTH Aachen University, Aachen, Germany.
authors.forename: Günther
authors.initials: G
authors.lastname: Schmalzing
authors.affiliation: Interdisciplinary Center for Clinical Research (IZKF), Medical Faculty of the RWTH Aachen University, Aachen, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Zwadlo-Klarwasser
authors.affiliation: Department of Dermatology and Allergology, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Jens Malte
authors.initials: JM
authors.lastname: Baron
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement; D048430:Cell Shape; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D017136:Ion Transport; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D027361:Organic Anion Transporters / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D014982:Xenopus laevis
chemical_list: D027361:Organic Anion Transporters; C551029:SLCO5A1 protein, human