PUBLICATION
Identification and Functional Characterization of Zebrafish Solute Carrier Slc16a2 (Mct8) as a Thyroid Hormone Membrane Transporter
- Authors
- Arjona, F.J., de Vrieze, E., Visser, T.J., Flik, G., and Klaren, P.H.
- ID
- ZDB-PUB-111013-5
- Date
- 2011
- Source
- Endocrinology 152(12): 5065-73 (Journal)
- Registered Authors
- Arjona, F.J., de Vrieze, Erik, Flik, Gert, Klaren, Peter
- Keywords
- none
- MeSH Terms
-
- Animals
- Biological Transport
- Cloning, Molecular
- Kinetics
- Membrane Transport Proteins/genetics
- Membrane Transport Proteins/metabolism
- Monocarboxylic Acid Transporters/genetics
- Monocarboxylic Acid Transporters/metabolism*
- Sequence Analysis
- Temperature
- Thyroid Hormones/metabolism*
- Tissue Distribution
- Triiodothyronine/metabolism
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 21952246 Full text @ Endocrinology
Citation
Arjona, F.J., de Vrieze, E., Visser, T.J., Flik, G., and Klaren, P.H. (2011) Identification and Functional Characterization of Zebrafish Solute Carrier Slc16a2 (Mct8) as a Thyroid Hormone Membrane Transporter. Endocrinology. 152(12):5065-73.
Abstract
Most components of the thyroid system in bony fish have been described and characterized, with the notable exception of thyroid
hormone membrane transporters. We have cloned, sequenced, and expressed the zebrafish solute carrier Slc16a2 (also named monocarboxylate transporter Mct8) cDNA and established its role as a thyroid hormone transport protein. The cloned cDNA shares 56–57% homology with its mammalian
orthologs. The 526-amino-acid sequence contains 12 predicted transmembrane domains. An intracellular N-terminal PEST domain,
thought to be involved in proteolytic processing of the protein, is present in the zebrafish sequence. Measured at initial
rate and at the body/rearing temperature of zebrafish (26 C), T3 uptake by zebrafish Slc16a2 is a saturable process with a calculated Michaelis-Menten constant of 0.8 μM T3. The rate of T3 uptake is temperature dependent and Na+ independent. Interestingly, at 26 C, zebrafish Slc16a2 does not transport T4. This implies that at a normal body temperature in zebrafish, Slc16a2 protein is predominantly involved in T3 uptake. When measured at 37 C, zebrafish Slc16a2 transports T4 in a Na+-independent manner. In adult zebrafish, the Slc16a2 gene is highly expressed in brain, gills, pancreas, liver, pituitary, heart, kidney, and gut. Beginning from the midblastula
stage, Slc16a2 is also expressed during zebrafish early development, the highest expression levels occurring 48 h after fertilization. This
is the first direct evidence for thyroid hormone membrane transporters in fish. We suggest that Slc16a2 plays a key role in
the local availability of T3 in adult tissues as well as during the completion of morphogenesis of primary organ systems.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping