{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC51B, which encodes the OSTβ subunit of the heteromeric organic solute transporter OSTα‑OSTβ, is essential for the basolateral transport of bile acids in epithelial tissues such as the small intestine, kidney, liver, adrenal gland, and testis. In these cells, OSTβ partners with OSTα to mediate the efflux of bile acids from enterocytes and other polarized cells, a process critical for enterohepatic circulation. Expression of this transporter is highly regulated by nuclear receptors—most notably the farnesoid X receptor (FXR)—which, upon bile acid binding, induces transcription of both subunits to adapt to cholestatic conditions and other metabolic stimuli. This coordinated regulation has been demonstrated in human and rodent tissues, as well as in various cell models."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, SLC51B is indispensable for the proper assembly, trafficking, and function of the OSTα‑OSTβ complex. Critical regions within the OSTβ protein, such as its transmembrane domain, conserved tryptophan–asparagine sequence, and a highly conserved dileucine motif within the extracellular N-terminal region, govern its physical interaction with OSTα and ensure the complex’s accurate localization to the plasma membrane. In addition, OSTβ expression is subject to further regulation by retinoic acid receptor and constitutive androstane receptor (via a novel DR5 response element) and epigenetic mechanisms—for example, modulation of histone acetylation by p300—which have been linked to disease states such as gallstone formation and colorectal cancer. These findings underscore a sophisticated level of control over OSTβ that is vital for maintaining bile acid homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in bile acid transport, the OSTα‑OSTβ complex, via its OSTβ component, also facilitates the movement of conjugated steroids—including dehydroepiandrosterone sulfate, pregnenolone sulfate, and estrone sulfate—highlighting its contribution to neurosteroid homeostasis and steroidogenesis. In renal proximal tubule cells, OSTβ-dependent uptake of estrone sulfate is critical for maintaining the local pool of nephroprotective estradiol, and diminished expression of SLC51B has been linked to pathologies such as renal dysfunction in MODY3 patients. Moreover, conditions such as hypoxia can influence OSTα‑OSTβ expression, further implicating this transporter in diverse physiological and pathophysiological processes. These expanded substrate specificities and regulatory mechanisms reveal a pleiotropic role for OSTβ in maintaining both bile acid and steroid solute balance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nazzareno Ballatori, Whitney V Christian, Jin Young Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "OSTalpha-OSTbeta: a major basolateral bile acid and steroid transporter in human intestinal, renal, and biliary epithelia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatology (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hep.20961"}], "href": "https://doi.org/10.1002/hep.20961"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16317684"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16317684"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "James L Boyer, Michael Trauner, Albert Mennone, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Upregulation of a basolateral FXR-dependent bile acid efflux transporter OSTalpha-OSTbeta in cholestasis in humans and rodents."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Gastrointest Liver Physiol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpgi.00539.2005"}], "href": "https://doi.org/10.1152/ajpgi.00539.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16423920"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16423920"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jean-François Landrier, Jyrki J Eloranta, Stephan R Vavricka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The nuclear receptor for bile acids, FXR, transactivates human organic solute transporter-alpha and -beta genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Gastrointest Liver Physiol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpgi.00430.2005"}], "href": "https://doi.org/10.1152/ajpgi.00430.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16269519"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16269519"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "David J Seward, Albert S Koh, James L Boyer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional complementation between a novel mammalian polygenic transport complex and an evolutionarily ancient organic solute transporter, OSTalpha-OSTbeta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M301106200"}], "href": "https://doi.org/10.1074/jbc.M301106200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12719432"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12719432"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hans Lee, Yanqiao Zhang, Florence Y Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FXR regulates organic solute transporters alpha and beta in the adrenal gland, kidney, and intestine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Lipid Res (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1194/jlr.M500417-JLR200"}], "href": "https://doi.org/10.1194/jlr.M500417-JLR200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16251721"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16251721"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Olga Renner, Simone Harsch, André Strohmeyer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reduced ileal expression of OSTalpha-OSTbeta in non-obese gallstone disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Lipid Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1194/jlr.M800162-JLR200"}], "href": "https://doi.org/10.1194/jlr.M800162-JLR200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18469300"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18469300"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "An-Qiang Sun, Natarajan Balasubramaniyan, Ke Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein-protein interactions and membrane localization of the human organic solute transporter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Gastrointest Liver Physiol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpgi.00457.2006"}], "href": "https://doi.org/10.1152/ajpgi.00457.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17332473"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17332473"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Whitney V Christian, Na Li, Patricia M Hinkle, et al. "}, {"type": "b", "children": [{"type": "t", "text": "β-Subunit of the Ostα-Ostβ organic solute transporter is required not only for heterodimerization and trafficking but also for function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.352245"}], "href": "https://doi.org/10.1074/jbc.M112.352245"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22535958"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22535958"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Carol J Soroka, Shuhua Xu, Albert Mennone, et al. "}, {"type": "b", "children": [{"type": "t", "text": "N-Glycosylation of the alpha subunit does not influence trafficking or functional activity of the human organic solute transporter alpha/beta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2121-9-57"}], "href": "https://doi.org/10.1186/1471-2121-9-57"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18847488"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18847488"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Shuhua Xu, An-Qiang Sun, Frederick J Suchy "}, {"type": "b", "children": [{"type": "t", "text": "A novel RARα/CAR-mediated mechanism for regulation of human organic solute transporter-β gene expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Gastrointest Liver Physiol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpgi.00138.2013"}], "href": "https://doi.org/10.1152/ajpgi.00138.2013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24264050"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24264050"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Shuhua Xu, Carol J Soroka, An-Qiang Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Novel Di-Leucine Motif at the N-Terminus of Human Organic Solute Transporter Beta Is Essential for Protein Association and Membrane Localization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0158269"}], "href": "https://doi.org/10.1371/journal.pone.0158269"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27351185"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27351185"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Ying Zhou, Chaonan Ye, Yan Lou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epigenetic Mechanisms Underlying Organic Solute Transporter "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "β"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Repression in Colorectal Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Pharmacol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/mol.119.118216"}], "href": "https://doi.org/10.1124/mol.119.118216"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32005758"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32005758"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Fang Fang, Whitney V Christian, Sadie G Gorman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neurosteroid transport by the organic solute transporter OSTα-OSTβ."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurochem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1471-4159.2010.06920.x"}], "href": "https://doi.org/10.1111/j.1471-4159.2010.06920.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20649839"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20649839"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Nazzareno Ballatori "}, {"type": "b", "children": [{"type": "t", "text": "Pleiotropic functions of the organic solute transporter Ostα-Ostβ."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dig Dis (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000324123"}], "href": "https://doi.org/10.1159/000324123"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21691099"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21691099"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Carlos A Schaffner, Jessica Mwinyi, Zhibo Gai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The organic solute transporters alpha and beta are induced by hypoxia in human hepatocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Liver Int (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/liv.12558"}], "href": "https://doi.org/10.1111/liv.12558"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24703425"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24703425"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Jun Wei Chan, Claire Wen Ying Neo, Soumita Ghosh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HNF1A binds and regulates the expression of SLC51B to facilitate the uptake of estrone sulfate in human renal proximal tubule epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-023-05827-8"}], "href": "https://doi.org/10.1038/s41419-023-05827-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37137894"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37137894"}]}]}]}