Phylogenetic, syntenic, and tissue expression analysis of slc22 genes in zebrafish (Danio rerio)

Abstract

BackgroundSLC22 protein family is a member of the SLC (Solute carriers) superfamily of polyspecific membrane transporters responsible for uptake of a wide range of organic anions and cations, including numerous endo- and xenobiotics. Due to the lack of knowledge on zebrafish Slc22 family, we performed initial characterization of these transporters using a detailed phylogenetic and conserved synteny analysis followed by the tissue specific expression profiling of slc22 transcripts.ResultsWe identified 20 zebrafish slc22 genes which are organized in the same functional subgroups as human SLC22 members. Orthologies and syntenic relations between zebrafish and other vertebrates revealed consequences of the teleost-specific whole genome duplication as shown through one-to-many orthologies for certain zebrafish slc22 genes. Tissue expression profiles of slc22 transcripts were analyzed using qRT-PCR determinations in nine zebrafish tissues: liver, kidney, intestine, gills, brain, skeletal muscle, eye, heart, and gonads. Our analysis revealed high expression of oct1 in kidney, especially in females, followed by oat3 and oat2c in females, oat2e in males and orctl4 in females. oct1 was also dominant in male liver. oat2d showed the highest expression in intestine with less noticeable gender differences. All slc22 genes showed low expression in gills, and moderate expression in heart and skeletal muscle. Dominant genes in brain were oat1 in females and oct1 in males, while the highest gender differences were determined in gonads, with dominant expression of almost all slc22 genes in testes and the highest expression of oat2a.ConclusionsOur study offers the first insight into the orthology relationships, gene expression and potential role of Slc22 membrane transporters in zebrafish. Clear orthological relationships of zebrafish slc22 and other vertebrate slc22 genes were established. slc22 members are mostly highly conserved, suggesting their physiological and toxicological importance. One-to-many orthologies and differences in tissue expression patterns of zebrafish slc22 genes in comparison to human orthologs were observed. Our expression data point to partial similarity of zebrafish versus human Slc22 members, with possible compensatory roles of certain zebrafish transporters, whereas higher number of some orthologs implies potentially more diverse and specific roles of these proteins in zebrafish.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2981-y) contains supplementary material, which is available to authorized users.

Effect of Cholesterol on the Organic Cation Transporter OCTN1 (SLC22A4)

“…OCTN1 belongs to a small sub-family of organic cation transporters that includes only three members, OCTN1, 2 and 3 [1,2]. However, the gene coding for OCTN3 was lost in humans [3,4], that possess only OCTN1 and OCTN2 [5]. Differently from OCTN2, which is a well-acknowledged carnitine transporter, human OCTN1 presents still uncertainties concerning the substrate specificity and, hence, the physiological role.…”

Effect-directed analysis reveals inhibition of zebrafish uptake transporter Oatp1d1 by caulerpenyne, a major secondary metabolite from the invasive marine alga Caulerpa taxifolia

“…We recently characterized the first uptake transporter of organic anions in zebrafish, named Oatp1d1, and demonstrated its interaction with various environmentally relevant compounds (Popovic et al, 2014). Continuing along this line of research, an uptake transporter of organic cations, Oct1, was also identified in zebrafish, and our first data indicated that Oct1 may function as an integral part of cellular defense against potentially hazardous organic endo-and xenobiotic cationic compounds through biliary and renal excretion (Mihaljevic et al, 2016).…”

Interaction between the zebrafish (Danio rerio) organic cation transporter 1 (Oct1) and endo- and xenobiotics

“…Phylogenetic and conserved synteny analysis revealed orthologous relationships between zebrafish genes -oct1 on chromosome 20 and oct2 on chromosome 17 -and the human OCT gene cluster on chromosome 6. Zebrafish Oct1 is highly expressed in the kidneys of both sexes as well as the male liver (Mihaljevic et al, 2016). The expression profile of Oct1 is similar to its human orthologs, OCT1 and OCT2, which are expressed in the basolateral membranes of the liver and kidney.…”

“…OCTs/Octs are highly conserved genes within vertebrate phyla, whose ancestry extends all the way to lamprey and sharks (Zhu et al, 2015). They are represented with three co-orthologs in reptiles, birds and humans, while in teleost fish and amphibians Octs have two and one ortholog(s), respectively (Mihaljevic et al, 2016). Mammalian OCT1-3/Oct1-3 are expressed in a number of toxicologically important tissues essential for metabolization and/or excretion of endo-and xenobiotics, especially liver and kidneys.…”

“…The structural and functional properties of fish Octs, along with their toxicological relevance, are still poorly understood. We have previously identified two zebrafish Oct genes, slc22a2 annotated as oct1, and slc22a3 annotated as oct2 (Mihaljevic et al, 2016). Phylogenetic and conserved synteny analysis revealed orthologous relationships between zebrafish genes -oct1 on chromosome 20 and oct2 on chromosome 17 -and the human OCT gene cluster on chromosome 6.…”