Related Experiment Video
Updated: Jun 24, 2025
10:08
Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting
Published on: December 9, 2022
2.1K
3,3',5-Triiodothyroacetic Acid Transporters
Zhongli Chen1, Sena Yildiz1, Boyka Markova2
1Department of Internal Medicine, Academic Centre for Thyroid Diseases, Erasmus University Medical Center Rotterdam, the Netherlands.
Summary
The study identified five human transporters (SLC10A1, SLCO1B1, SLC22A6, SLC22A8, SLC22A24) that efficiently transport the thyroid hormone analog TRIAC, crucial for treating MCT8 deficiency.
Area of Science:
- Biochemistry
- Molecular Biology
- Neuroendocrinology
Background:
- Thyroid hormone transporters are vital for cellular uptake of thyroid hormones.
- Monocarboxylate transporter (MCT) 8 deficiency causes severe neurodevelopmental issues due to impaired thyroid hormone transport.
- The thyroid hormone analog TRIAC shows therapeutic potential in MCT8 deficiency models and patients, but its transporters are unknown.
Purpose of the Study:
- To identify the specific transporters responsible for the cellular uptake of TRIAC.
- To screen candidate transporters expressed at the human blood-brain barrier (BBB) and/or brain-cerebrospinal fluid barrier.
- To investigate the transport activity of known thyroid hormone transporters for TRIAC.
Main Methods:
- Screened 59 plasma membrane transporters for TRIAC accumulation in COS-1 cells.
- Utilized cell surface biotinylation assays to confirm plasma membrane expression.
- Assessed TRIAC uptake in various media conditions (DPBS/glucose, DMEM with/without BSA).
- Examined orthologs in zebrafish and mice, and Slc22a8 expression in mouse brain tissue.
Main Results:
- Eighteen transporters facilitated significant TRIAC intracellular accumulation under basal conditions.
- SLCO1B1, SLC22A8, SLC10A1, SLC22A6, and SLC22A24 demonstrated substantial TRIAC transport, particularly in the presence of BSA.
- Orthologs in zebrafish and mice also efficiently transported TRIAC.
- Slc22a8 showed high expression in mouse brain capillary endothelial and choroid plexus cells during early development.
Conclusions:
- Human SLC10A1, SLCO1B1, SLC22A6, SLC22A8, and SLC22A24 are identified as efficient TRIAC transporters.
- These findings enhance understanding of TRIAC's mechanism of action in MCT8 deficiency.
- This knowledge is critical for optimizing TRIAC-based therapies for patients with MCT8 deficiency and related conditions.
More Related Videos
11:34A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
2.2K
06:18Brain Slice Biotinylation: An Ex Vivo Approach to Measure Region-specific Plasma Membrane Protein Trafficking in Adult Neurons
Published on: April 3, 2014
12.9K
Related Concept Videos
01:27ABC Transporters: Importer
2.7K
ATP-binding cassette or ABC transporters are a class of ATP-driven pumps that hydrolyze ATP to move solutes across the membrane. They can be grouped into importers and exporters. While exporters are present in all domains of life, importers exist only in bacteria and some plants.
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
2.7K
01:06Carrier-Mediated Transport
355
Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
355
01:31ABC Transporters: Exporter
4.3K
ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
4.3K
01:31Membrane Transporters
10.7K
Transporters are essential membrane transport proteins with functions related to cell nutrition, homeostasis, communication, etc. Approximately 7% of all genes in the human genome code for transporters or transporter-related proteins.
Transporters are mainly composed of alpha-helices, built from bundles of ten or more helices traversing the plasma membrane. The solute-binding sites are located midway, where some of the helices are broken or distorted, making space for the binding site through...
Transporters are mainly composed of alpha-helices, built from bundles of ten or more helices traversing the plasma membrane. The solute-binding sites are located midway, where some of the helices are broken or distorted, making space for the binding site through...
10.7K
01:14Active Transport
611
Active transport is a critical biological process that allows cells to move solutes against an electrochemical gradient. This process requires direct energy input and is characterized by its selectivity, saturability, and susceptibility to competitive inhibition.
Primary active transporters, like Na+, K+ and -ATPase, directly utilize ATP to move ions across the membrane. These transporters play significant roles in various physiological processes. For instance, Na+, K+ and -ATPase maintain...
Primary active transporters, like Na+, K+ and -ATPase, directly utilize ATP to move ions across the membrane. These transporters play significant roles in various physiological processes. For instance, Na+, K+ and -ATPase maintain...
611
01:14Hepatic Drug Clearance: Role of Transporters
54
In the liver and bile canaliculi, influx and efflux transporters modification can influence intrinsic clearance. Transporters play a significant role in moving drugs within liver cells. Elaborate models, such as the Biopharmaceutical Classification System (BCS), are essential to relate transporters to drug disposition. This system categorizes drugs into four classes based on solubility and permeability, providing insights into elimination routes and the effects of transporters following oral...
54