engleski

Molecular characterization of zebrafish Oatp1d1 (Slco1d1), a novel Organic anion transporting polypeptide

Organic anion transporting polypeptide (OATP/Oatp) superfamily includes group of polyspecific transporters that mediate transport of large amphipathic, mostly anionic molecules across cell membranes of eukaryotes. OATPs/Oatps are involved in disposition and elimination of numerous physiological and foreign compounds. However, in non-mammalian species functional properties of Oatps remain unknown. We aimed to elucidate the role of Oatp1d1 in zebrafish to gain insights into the functional and structural evolution of the OATP1/Oatp1 superfamily. We show that diversification of the OATP1/Oatp1 family occurs after the emergence of jawed fish and that OATP1A/Oatp1a and OATP1B/Oatp1b subfamilies appeared at the root of tetrapods. The Oatp1d subfamily emerged in teleosts and is absent in tetrapods. The zebrafish Oatp1d1 is similar to mammalian OATP1A/Oatp1a and OATP1B/Oatp1b members, with the main physiological role in transport and balance of steroid hormones. Oatp1d1 activity is dependent upon pH gradient which could indicate bicarbonate exchange as a mode of transport. Our analysis of evolutionary conservation and structural properties revealed that: (i) H79 in the intracellular loop 3 is conserved within OATP1/Oatp1 family and is crucial for the transport activity ; (ii) N-glycosylation impacts membrane targeting and is conserved within the OATP1/Oatp1 family with N122, N133, N499 and N512 residues involved ; (iii) evolutionary conserved CRAC motif is important for membrane localization ; and (iv) Oatp1d1 is present in dimeric and possibly oligomeric form in the cell membrane. In conclusion, we describe the first detailed characterization of a new Oatp transporter in zebrafish, offering important insights into the functional evolution of OATP1/Oatp1 family and the physiological role of Oatp1d1.

OATP/Oatp; zebrafish Oatp1d1; phylogeny; substrate specificity; physiological role

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