ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2011
PDZK1 binding and serine phosphorylation regulate subcellular trafficking of organic anion transport protein 1a1.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Subcellular activation of β-adrenergic receptors using a spatially restricted antagonist.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Oligomerization of drug transporters: Forms, functions, and mechanisms.Acta pharmaceutica Sinica. B · 2024Review
- Interaction of Human OATP1B1 with PDZK1 Is Required for Its Trafficking to the Hepatocyte Plasma Membrane.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Increased/Targeted Brain (Pro)Drug Delivery via Utilization of Solute Carriers (SLCs).Pharmaceutics · 2022Review
- A guide to plasma membrane solute carrier proteins.The FEBS journal · 2021Review
- Post-translational regulation of the major drug transporters in the families of organic anion transporters and organic anion-transporting polypeptides.The Journal of biological chemistry · 2020Review
- Interindividual Diversity in Expression of Organic Anion Uptake Transporters in Normal and Cirrhotic Human Liver.Hepatology communications · 2020Article
- Rat Organic Anion Transport Protein 1A1 Interacts Directly With Organic Anion Transport Protein 1A4 Facilitating Its Maturation and Trafficking to the Hepatocyte Plasma Membrane.Hepatology (Baltimore, Md.) · 2019Article
- Loops and layers of post-translational modifications of drug transporters.Advanced drug delivery reviews · 2017Review
- The Na(+)-Taurocholate Cotransporting Polypeptide Traffics with the Epidermal Growth Factor Receptor.Traffic (Copenhagen, Denmark) · 2016Article
- Drug Transporters and Na+/H+ Exchange Regulatory Factor PSD-95/Drosophila Discs Large/ZO-1 Proteins.Pharmacological reviews · 2015Review
- Organic anion uptake by hepatocytes.Comprehensive Physiology · 2014Review
- Role of protein kinase C isoforms in bile formation and cholestasis.Hepatology (Baltimore, Md.) · 2014Review
- Hypoxia/reoxygenation stress signals an increase in organic anion transporting polypeptide 1a4 (Oatp1a4) at the blood-brain barrier: relevance to CNS drug delivery.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2014Article
- Oatp1a1 requires PDZK1 to traffic to the plasma membrane by selective recruitment of microtubule-based motor proteins.Drug metabolism and disposition: the biological fate of chemicals · 2014Article
- Article
- Hepatocyte polarity.Comprehensive Physiology · 2013Review
- OATPs, OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies.British journal of pharmacology · 2012Review
- The expression and function of organic anion transporting polypeptides in normal tissues and in cancer.Annual review of pharmacology and toxicology · 2012Review
- Isolation of modulators of the liver-specific organic anion-transporting polypeptides (OATPs) 1B1 and 1B3 from Rollinia emarginata Schlecht (Annonaceae).The Journal of pharmacology and experimental therapeutics · 2011Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Although perturbation of organic anion transport protein (oatp) cell surface expression can result in drug toxicity, little is known regarding mechanisms regulating its subcellular distribution. Many members of the oatp family, including oatp1a1, have a COOH-terminal PDZ consensus binding motif that interacts with PDZK1, while serines upstream of this site (S634 and S635) can be phosphorylated. Using oatp1a1 as a prototypical member of the oatp family, we prepared plasmids in which these serines were mutated to glutamic acid [E634E635 (oatp1a1(EE)), phosphomimetic] or alanine [A634A635 (oatp1a1(AA)), nonphosphorylatable]. Distribution of oatp1a1(AA) and oatp1a1(EE) was largely intracellular in transfected human embryonic kidney (HEK) 293T cells. Cotransfection with a plasmid encoding PDZK1 revealed that oatp1a1(AA) was now expressed largely on the cell surface, while oatp1a1(EE) remained intracellular. To quantify these changes, studies were performed in HuH7 cells stably transfected with these oatp1a1 plasmids. These cells endogenously express PDZK1. Surface biotinylation at 4°C followed by shift to 37°C showed that oatp1a1(EE) internalizes quickly compared with oatp1a1(AA). To examine a physiological role for phosphorylation in oatp1a1 subcellular distribution, studies were performed in rat hepatocytes exposed to extracellular ATP, a condition that stimulates serine phosphorylation of oatp1a1 via activity of a purinergic receptor. Internalization of oatp1a1 under these conditions was rapid. Thus, although PDZK1 binding is required for optimal cell surface expression of oatp1a1, phosphorylation provides a mechanism for fast regulation of the distribution of oatp1a1 between the cell surface and intracellular vesicular pools. Identification of the proteins and motor molecules that mediate these trafficking events represents an important area for future study.
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