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Cloning and characterization of a novel functional organic anion transporting polypeptide 3A1 isoform highly expressed in the human brain and testis

Organic anion transporting polypeptide 3A1 (OATP3A1, encoded by the SLCO3A1 gene) is a prostaglandin, oligopeptide, and steroid/thyroid hormone transporter with wide tissue distribution, expressed, e.g., in the human brain and testis. Although the physiological importance of OATP3A1 has not yet been...

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Autores principales: Bakos, Éva, Német, Orsolya, Kucsma, Nóra, Tőkési, Natália, Stieger, Bruno, Rushing, Elisabeth, Tőkés, Anna-Mária, Kele, Péter, Tusnády, Gábor E., Özvegy-Laczka, Csilla
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9479004/
https://www.ncbi.nlm.nih.gov/pubmed/36120371
http://dx.doi.org/10.3389/fphar.2022.958023
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author Bakos, Éva
Német, Orsolya
Kucsma, Nóra
Tőkési, Natália
Stieger, Bruno
Rushing, Elisabeth
Tőkés, Anna-Mária
Kele, Péter
Tusnády, Gábor E.
Özvegy-Laczka, Csilla
author_facet Bakos, Éva
Német, Orsolya
Kucsma, Nóra
Tőkési, Natália
Stieger, Bruno
Rushing, Elisabeth
Tőkés, Anna-Mária
Kele, Péter
Tusnády, Gábor E.
Özvegy-Laczka, Csilla
author_sort Bakos, Éva
collection PubMed
description Organic anion transporting polypeptide 3A1 (OATP3A1, encoded by the SLCO3A1 gene) is a prostaglandin, oligopeptide, and steroid/thyroid hormone transporter with wide tissue distribution, expressed, e.g., in the human brain and testis. Although the physiological importance of OATP3A1 has not yet been clarified, based on its expression pattern, substrate recognition, and evolutionary conservation, OATP3A1 is a potential pharmacological target. Previously, two isoforms of OATP3A1, termed as V1 and V2, have been characterized. Here, we describe the cloning and functional characterization of a third isoform, OATP3A1_V3. The mRNA of isoform V3 is formed by alternative splicing and results in an OATP3A1 protein with an altered C-terminus compared to isoforms V1 and V2. Based on quantitative PCR, we demonstrate the widespread expression of SLCO3A1_V3 mRNA in human organs, with the highest expression in the brain and testis. By generation of an isoform V3-specific antibody and immunostaining, we show that the encoded protein is expressed in the human choroid plexus, neurons, and both germ and Sertoli cells of the testis. Moreover, we demonstrate that in contrast to isoform V1, OATP3A1_V3 localizes to the apical membrane of polarized MDCKII cells. Using HEK-293 cells engineered to overexpress OATP3A1_V3, we verify the protein’s functionality and identify dehydroepiandrosterone sulfate as a novel OATP3A1 substrate. Based on their distinct expression patterns but overlapping functions, OATP3A1 isoforms may contribute to transcellular (neuro)steroid transport in the central nervous system.
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spelling pubmed-94790042022-09-17 Cloning and characterization of a novel functional organic anion transporting polypeptide 3A1 isoform highly expressed in the human brain and testis Bakos, Éva Német, Orsolya Kucsma, Nóra Tőkési, Natália Stieger, Bruno Rushing, Elisabeth Tőkés, Anna-Mária Kele, Péter Tusnády, Gábor E. Özvegy-Laczka, Csilla Front Pharmacol Pharmacology Organic anion transporting polypeptide 3A1 (OATP3A1, encoded by the SLCO3A1 gene) is a prostaglandin, oligopeptide, and steroid/thyroid hormone transporter with wide tissue distribution, expressed, e.g., in the human brain and testis. Although the physiological importance of OATP3A1 has not yet been clarified, based on its expression pattern, substrate recognition, and evolutionary conservation, OATP3A1 is a potential pharmacological target. Previously, two isoforms of OATP3A1, termed as V1 and V2, have been characterized. Here, we describe the cloning and functional characterization of a third isoform, OATP3A1_V3. The mRNA of isoform V3 is formed by alternative splicing and results in an OATP3A1 protein with an altered C-terminus compared to isoforms V1 and V2. Based on quantitative PCR, we demonstrate the widespread expression of SLCO3A1_V3 mRNA in human organs, with the highest expression in the brain and testis. By generation of an isoform V3-specific antibody and immunostaining, we show that the encoded protein is expressed in the human choroid plexus, neurons, and both germ and Sertoli cells of the testis. Moreover, we demonstrate that in contrast to isoform V1, OATP3A1_V3 localizes to the apical membrane of polarized MDCKII cells. Using HEK-293 cells engineered to overexpress OATP3A1_V3, we verify the protein’s functionality and identify dehydroepiandrosterone sulfate as a novel OATP3A1 substrate. Based on their distinct expression patterns but overlapping functions, OATP3A1 isoforms may contribute to transcellular (neuro)steroid transport in the central nervous system. Frontiers Media S.A. 2022-09-02 /pmc/articles/PMC9479004/ /pubmed/36120371 http://dx.doi.org/10.3389/fphar.2022.958023 Text en Copyright © 2022 Bakos, Német, Kucsma, Tőkési, Stieger, Rushing, Tőkés, Kele, Tusnády and Özvegy-Laczka. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Bakos, Éva
Német, Orsolya
Kucsma, Nóra
Tőkési, Natália
Stieger, Bruno
Rushing, Elisabeth
Tőkés, Anna-Mária
Kele, Péter
Tusnády, Gábor E.
Özvegy-Laczka, Csilla
Cloning and characterization of a novel functional organic anion transporting polypeptide 3A1 isoform highly expressed in the human brain and testis
title Cloning and characterization of a novel functional organic anion transporting polypeptide 3A1 isoform highly expressed in the human brain and testis
title_full Cloning and characterization of a novel functional organic anion transporting polypeptide 3A1 isoform highly expressed in the human brain and testis
title_fullStr Cloning and characterization of a novel functional organic anion transporting polypeptide 3A1 isoform highly expressed in the human brain and testis
title_full_unstemmed Cloning and characterization of a novel functional organic anion transporting polypeptide 3A1 isoform highly expressed in the human brain and testis
title_short Cloning and characterization of a novel functional organic anion transporting polypeptide 3A1 isoform highly expressed in the human brain and testis
title_sort cloning and characterization of a novel functional organic anion transporting polypeptide 3a1 isoform highly expressed in the human brain and testis
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9479004/
https://www.ncbi.nlm.nih.gov/pubmed/36120371
http://dx.doi.org/10.3389/fphar.2022.958023
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