Biology:Monocarboxylate transporter 8
 Generic protein structure example |
Monocarboxylate transporter 8 (MCT8) is an active transporter protein that in humans is encoded by the SLC16A2 gene.[1][2][3][4]
Function
MCT8 actively transports a variety of iodo-thyronines including the thyroid hormones T3 and T4.[2]
Clinical significance
A genetic disorder (discovered in 2003[2] and 2004[5]) 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/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.[6] Some of the symptoms for this disorder as are follows: normal to slightly elevated TSH, elevated T3 and reduced T4 (ratio of T3/T4 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, known as PMD[7]), 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/T4/T3 thyroid test.
Model organisms
Zebrafish
A knockout zebrafish line was generated in 2014 using the zinc-finger nuclease (ZFN)-mediated targeted gene editing system.[8] Similar to human patients, the zebrafish larvae exhibited neurological and behavioral deficiencies. They demonstrated reduced locomotor activity, altered myelin-related genes and neuron-specific deficiencies in circuit formation.[9]
Xenopus
Expression of mct8 has been characterised in Xenopus laevis[10] and Xenopus tropicalis.[11]
See also
References
- ↑ "A novel transmembrane transporter encoded by the XPCT gene in Xq13.2". Human Molecular Genetics 3 (7): 1133–9. Jul 1994. doi:10.1093/hmg/3.7.1133. PMID 7981683.
- ↑ 2.0 2.1 2.2 "Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter". The Journal of Biological Chemistry 278 (41): 40128–35. Oct 2003. doi:10.1074/jbc.M300909200. PMID 12871948.
- ↑ "Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene". American Journal of Human Genetics 77 (1): 41–53. Jul 2005. doi:10.1086/431313. PMID 15889350.
- ↑ "Entrez Gene: SLC16A2 solute carrier family 16, member 2 (monocarboxylic acid transporter 8)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6567.
- ↑ "A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene". American Journal of Human Genetics 74 (1): 168–75. Jan 2004. doi:10.1086/380999. PMID 14661163.
- ↑ "Rapid detection of a mutation causing X-linked leucoencephalopathy by exome sequencing". Journal of Medical Genetics 48 (9): 606–9. Sep 2011. doi:10.1136/jmg.2010.083535. PMID 21415082.
- ↑ "Pelizaeus-Merzbacher-Like disease presentation of MCT8 mutated male subjects". Annals of Neurology 65 (1): 114–8. Jan 2009. doi:10.1002/ana.21579. PMID 19194886.
- ↑ "Altered behavioral performance and live imaging of circuit-specific neural deficiencies in a zebrafish model for psychomotor retardation". PLOS Genetics 10 (9): e1004615. Sep 2014. doi:10.1371/journal.pgen.1004615. PMID 25255244.
- ↑ "Altered behavioral performance and live imaging of circuit-specific neural deficiencies in a zebrafish model for psychomotor retardation". PLOS Genetics 10 (9): e1004615. Sep 2014. doi:10.1371/journal.pgen.1004615. PMID 25255244.
- ↑ Mughal, Bilal B.; Leemans, Michelle; Lima de Souza, Elaine C.; le Mevel, Sébastien; Spirhanzlova, Petra; Visser, Theo J.; Fini, Jean-Baptiste; Demeneix, Barbara A. (2017-08-01). "Functional Characterization of Xenopus Thyroid Hormone Transporters mct8 and oatp1c1". Endocrinology 158 (8): 2694–2705. doi:10.1210/en.2017-00108. ISSN 1945-7170. PMID 28591769.
- ↑ Connors, Kristin A.; Korte, Joseph J.; Anderson, Grant W.; Degitz, Sigmund J. (2010-08-01). "Characterization of thyroid hormone transporter expression during tissue-specific metamorphic events in Xenopus tropicalis". General and Comparative Endocrinology 168 (1): 149–159. doi:10.1016/j.ygcen.2010.04.015. ISSN 1095-6840. PMID 20417208.
Further reading
- "The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond". Pflügers Archiv 447 (5): 619–28. Feb 2004. doi:10.1007/s00424-003-1067-2. PMID 12739169.
- "Mechanisms of disease: psychomotor retardation and high T3 levels caused by mutations in monocarboxylate transporter 8". Nature Clinical Practice Endocrinology & Metabolism 2 (9): 512–23. Sep 2006. doi:10.1038/ncpendmet0262. PMID 16957765.
- "Thyroid hormone transporter defects". Endocrine Development 10: 118–26. 2007. doi:10.1159/000106823. ISBN 978-3-8055-8296-4. PMID 17684393.
- "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry 236 (1): 107–13. Apr 1996. doi:10.1006/abio.1996.0138. PMID 8619474.
- "Large-scale concatenation cDNA sequencing". Genome Research 7 (4): 353–8. Apr 1997. doi:10.1101/gr.7.4.353. PMID 9110174.
- "Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past". The Biochemical Journal 329 (2): 321–8. Jan 1998. doi:10.1042/bj3290321. PMID 9425115.
- "Cloning and localization of the murine Xpct gene: evidence for complex rearrangements during the evolution of the region around the Xist gene". Genomics 48 (3): 296–303. Mar 1998. doi:10.1006/geno.1997.5173. PMID 9545634.
- "A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene". American Journal of Human Genetics 74 (1): 168–75. Jan 2004. doi:10.1086/380999. PMID 14661163.
- "Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation". Lancet 364 (9443): 1435–7. 2004. doi:10.1016/S0140-6736(04)17226-7. PMID 15488219.
- "The monocarboxylate transporter 8 linked to human psychomotor retardation is highly expressed in thyroid hormone-sensitive neuron populations". Endocrinology 146 (4): 1701–6. Apr 2005. doi:10.1210/en.2004-1179. PMID 15661862.
- "X-linked paroxysmal dyskinesia and severe global retardation caused by defective MCT8 gene". Journal of Neurology 252 (6): 663–6. Jun 2005. doi:10.1007/s00415-005-0713-3. PMID 15834651.
- "Thyroid hormone transport by the human monocarboxylate transporter 8 and its rate-limiting role in intracellular metabolism". Molecular Endocrinology 20 (11): 2761–72. Nov 2006. doi:10.1210/me.2005-0256. PMID 16887882.
- "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell 127 (3): 635–48. Nov 2006. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
- "Functional analysis of monocarboxylate transporter 8 mutations identified in patients with X-linked psychomotor retardation and elevated serum triiodothyronine". The Journal of Clinical Endocrinology and Metabolism 92 (6): 2378–81. Jun 2007. doi:10.1210/jc.2006-2570. PMID 17356046.
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