Monocarboxylate transporter 8 (MCT8) is an active transporter
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''SLC16A2''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Function
MCT8 actively transports a variety of iodo-
thyronines including the thyroid hormones
T3 and
T4.
Clinical significance
A genetic disorder (discovered in 2003
and 2004
) is caused by mutation in the transporter of thyroid hormone, MCT8, also known as SLC16A2, is believed to be account for a significant fraction of the undiagnosed neurological disorders (usually resulting in
hypotonic
In chemical biology, tonicity is a measure of the effective osmotic pressure gradient; the water potential of two solutions separated by a partially-permeable cell membrane. Tonicity depends on the relative concentration of selective memb ...
/floppy infants with delayed milestones). This genetic defect was known as
Allan–Herndon–Dudley syndrome (since 1944) without knowing its actual cause. It has been shown mutated in cases of X-linked
leukoencephalopathy.
Some of the symptoms for this disorder as are follows: normal to slightly elevated
TSH, elevated T
3 and reduced T
4 (ratio of T
3/T
4 is about double its normal value). Normal looking at birth and for the first few years, hypotonic (floppy), in particular difficulty to hold the head, possibly difficulty to thrive, possibly with delayed myelination (if so, some cases are reported with an MRI pattern similar to
Pelizaeus–Merzbacher disease
Pelizaeus–Merzbacher disease is an X-linked neurological disorder that damages oligodendrocytes in the central nervous system. It is caused by mutations in proteolipid protein 1 (''PLP1''), a major myelin protein. It is characterized by a decr ...
, known as PMD
), possibly with decreased mitochondrial enzyme activities, possibly with fluctuating
lactate level. Patients have an alert face, a limited IQ, patients may never talk/walk, 50% need feeding tube, patients have a normal life span. This disease can be ruled out with a simple TSH/T
4/T
3 thyroid test.
Model organisms
Zebrafish
A knockout
zebrafish
The zebrafish (''Danio rerio'') is a species of freshwater ray-finned fish belonging to the family Danionidae of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (an ...
line was generated in 2014 using the
zinc-finger nuclease (ZFN)-mediated targeted gene editing system. Similar to human patients, ''the'' zebrafish larvae exhibited neurological and behavioral deficiencies. They demonstrated reduced locomotor activity, altered
myelin
Myelin Sheath ( ) is a lipid-rich material that in most vertebrates surrounds the axons of neurons to insulate them and increase the rate at which electrical impulses (called action potentials) pass along the axon. The myelinated axon can be lik ...
-related genes and neuron-specific deficiencies in circuit formation.
''Xenopus''
Expression of ''mct8'' has been characterised in ''
Xenopus laevis
The African clawed frog (''Xenopus laevis''), also known as simply xenopus, African clawed toad, African claw-toed frog or the ''platanna'') is a species of African aquatic frog of the family Pipidae. Its name is derived from the short black ...
'' and ''
Xenopus tropicalis
The western clawed frog (''Xenopus tropicalis'') is a species of frog in the family Pipidae, also known as tropical clawed frog. It is the only species in the genus ''Xenopus'' to have a diploid genome. Its genome has been sequenced, making it a ...
''.
See also
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Solute carrier family
The solute carrier (SLC) group of membrane transport proteins include over 400 members organized into 66 families. Most members of the SLC group are located in the cell membrane. The SLC gene nomenclature system was originally proposed by the HUGO ...
References
Further reading
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{{Membrane transport proteins
Solute carrier family
Genes mutated in mice
Thyroid hormone transporters