monocarboxylate transporter 8
{{Short description|Protein-coding gene in the species Homo sapiens}}
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{{Infobox_gene}}
Monocarboxylate transporter 8 (MCT8) is an active transporter protein that in humans is encoded by the SLC16A2 gene.{{cite journal | vauthors = Lafrenière RG, Carrel L, Willard HF | title = A novel transmembrane transporter encoded by the XPCT gene in Xq13.2 | journal = Human Molecular Genetics | volume = 3 | issue = 7 | pages = 1133–1139 | date = Jul 1994 | pmid = 7981683 | doi = 10.1093/hmg/3.7.1133 }}{{cite journal | vauthors = Friesema EC, Ganguly S, Abdalla A, Manning Fox JE, Halestrap AP, Visser TJ | title = Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter | journal = The Journal of Biological Chemistry | volume = 278 | issue = 41 | pages = 40128–40135 | date = Oct 2003 | pmid = 12871948 | doi = 10.1074/jbc.M300909200 | doi-access = free }}{{cite journal | vauthors = Schwartz CE, May MM, Carpenter NJ, Rogers RC, Martin J, Bialer MG, Ward J, Sanabria J, Marsa S, Lewis JA, Echeverri R, Lubs HA, Voeller K, Simensen RJ, Stevenson RE | title = Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene | journal = American Journal of Human Genetics | volume = 77 | issue = 1 | pages = 41–53 | date = Jul 2005 | pmid = 15889350 | pmc = 1226193 | doi = 10.1086/431313 }}{{cite web | title = Entrez Gene: SLC16A2 solute carrier family 16, member 2 (monocarboxylic acid transporter 8) | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6567 }}
Function
Clinical significance
A genetic disorder (discovered in 2003 and 2004{{cite journal | vauthors = Dumitrescu AM, Liao XH, Best TB, Brockmann K, Refetoff S | title = A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene | journal = American Journal of Human Genetics | volume = 74 | issue = 1 | pages = 168–175 | date = Jan 2004 | pmid = 14661163 | pmc = 1181904 | doi = 10.1086/380999 }}) 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.{{cite journal | vauthors = Tsurusaki Y, Osaka H, Hamanoue H, Shimbo H, Tsuji M, Doi H, Saitsu H, Matsumoto N, Miyake N | title = Rapid detection of a mutation causing X-linked leucoencephalopathy by exome sequencing | journal = Journal of Medical Genetics | volume = 48 | issue = 9 | pages = 606–609 | date = Sep 2011 | pmid = 21415082 | doi = 10.1136/jmg.2010.083535 | s2cid = 1157351 }} 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{{cite journal | vauthors = Vaurs-Barrière C, Deville M, Sarret C, Giraud G, Des Portes V, Prats-Viñas JM, De Michele G, Dan B, Brady AF, Boespflug-Tanguy O, Touraine R | title = Pelizaeus-Merzbacher-Like disease presentation of MCT8 mutated male subjects | journal = Annals of Neurology | volume = 65 | issue = 1 | pages = 114–118 | date = Jan 2009 | pmid = 19194886 | doi = 10.1002/ana.21579 | s2cid = 27740314 }}), 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.{{cite journal | vauthors = Zada D, Tovin A, Lerer-Goldshtein T, Vatine GD, Appelbaum L | title = Altered behavioral performance and live imaging of circuit-specific neural deficiencies in a zebrafish model for psychomotor retardation | journal = PLOS Genetics | volume = 10 | issue = 9 | pages = e1004615 | date = Sep 2014 | pmid = 25255244 | pmc = 4177677 | doi = 10.1371/journal.pgen.1004615 | doi-access = free }} 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.{{cite journal | vauthors = Zada D, Tovin A, Lerer-Goldshtein T, Vatine GD, Appelbaum L | title = Altered behavioral performance and live imaging of circuit-specific neural deficiencies in a zebrafish model for psychomotor retardation | journal = PLOS Genetics | volume = 10 | issue = 9 | pages = e1004615 | date = Sep 2014 | pmid = 25255244 | pmc = 4177677 | doi = 10.1371/journal.pgen.1004615 | doi-access = free }}
= ''Xenopus'' =
Expression of mct8 has been characterised in Xenopus laevis{{Cite journal | vauthors = Mughal BB, Leemans M, Lima de Souza EC, le Mevel S, Spirhanzlova P, Visser TJ, Fini JB, Demeneix BA | title = Functional Characterization of Xenopus Thyroid Hormone Transporters mct8 and oatp1c1 | journal = Endocrinology | volume = 158 | issue = 8 | pages = 2694–2705 | date = 2017-08-01 | pmid = 28591769 | doi = 10.1210/en.2017-00108 | issn = 1945-7170 | doi-access = free }} and Xenopus tropicalis.{{Cite journal | vauthors = Connors KA, Korte JJ, Anderson GW, Degitz SJ | title = Characterization of thyroid hormone transporter expression during tissue-specific metamorphic events in Xenopus tropicalis | journal = General and Comparative Endocrinology | volume = 168 | issue = 1 | pages = 149–159 | date = 2010-08-01 | pmid = 20417208 | doi = 10.1016/j.ygcen.2010.04.015 | issn = 1095-6840 }}
See also
References
{{reflist|33em}}
Further reading
{{refbegin|33em}}
- {{cite journal | vauthors = Halestrap AP, Meredith D | title = The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond | journal = Pflügers Archiv: European Journal of Physiology | volume = 447 | issue = 5 | pages = 619–628 | date = Feb 2004 | pmid = 12739169 | doi = 10.1007/s00424-003-1067-2 | s2cid = 15498611 }}
- {{cite journal | vauthors = Friesema EC, Jansen J, Heuer H, Trajkovic M, Bauer K, Visser TJ | title = Mechanisms of disease: psychomotor retardation and high T3 levels caused by mutations in monocarboxylate transporter 8 | journal = Nature Clinical Practice. Endocrinology & Metabolism | volume = 2 | issue = 9 | pages = 512–523 | date = Sep 2006 | pmid = 16957765 | doi = 10.1038/ncpendmet0262 | s2cid = 25232696 }}
- {{cite journal | vauthors = Grüters A | title = Thyroid hormone transporter defects | journal = Endocrine Development | volume = 10 | pages = 118–126 | year = 2007 | pmid = 17684393 | doi = 10.1159/000106823 | isbn = 978-3-8055-8296-4 }}
- {{cite journal | vauthors = Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA | title = A "double adaptor" method for improved shotgun library construction | journal = Analytical Biochemistry | volume = 236 | issue = 1 | pages = 107–113 | date = Apr 1996 | pmid = 8619474 | doi = 10.1006/abio.1996.0138 }}
- {{cite journal | vauthors = Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA | title = Large-scale concatenation cDNA sequencing | journal = Genome Research | volume = 7 | issue = 4 | pages = 353–358 | date = Apr 1997 | pmid = 9110174 | pmc = 139146 | doi = 10.1101/gr.7.4.353 }}
- {{cite journal | vauthors = Price NT, Jackson VN, Halestrap AP | title = Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past | journal = The Biochemical Journal | volume = 329 | issue = 2 | pages = 321–328 | date = Jan 1998 | pmid = 9425115 | pmc = 1219047 | doi = 10.1042/bj3290321 }}
- {{cite journal | vauthors = Debrand E, Heard E, Avner P | title = Cloning and localization of the murine Xpct gene: evidence for complex rearrangements during the evolution of the region around the Xist gene | journal = Genomics | volume = 48 | issue = 3 | pages = 296–303 | date = Mar 1998 | pmid = 9545634 | doi = 10.1006/geno.1997.5173 }}
- {{cite journal | vauthors = Dumitrescu AM, Liao XH, Best TB, Brockmann K, Refetoff S | title = A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene | journal = American Journal of Human Genetics | volume = 74 | issue = 1 | pages = 168–175 | date = Jan 2004 | pmid = 14661163 | pmc = 1181904 | doi = 10.1086/380999 }}
- {{cite journal | vauthors = Friesema EC, Grueters A, Biebermann H, Krude H, von Moers A, Reeser M, Barrett TG, Mancilla EE, Svensson J, Kester MH, Kuiper GG, Balkassmi S, Uitterlinden AG, Koehrle J, Rodien P, Halestrap AP, Visser TJ | title = Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation | journal = Lancet | location = London, England | volume = 364 | issue = 9443 | pages = 1435–1437 | year = 2004 | pmid = 15488219 | doi = 10.1016/S0140-6736(04)17226-7 | s2cid = 37520843 | url = https://repositorio.uchile.cl/handle/2250/164655 }}
- {{cite journal | vauthors = Heuer H, Maier MK, Iden S, Mittag J, Friesema EC, Visser TJ, Bauer K | title = The monocarboxylate transporter 8 linked to human psychomotor retardation is highly expressed in thyroid hormone-sensitive neuron populations | journal = Endocrinology | volume = 146 | issue = 4 | pages = 1701–1706 | date = Apr 2005 | pmid = 15661862 | doi = 10.1210/en.2004-1179 | doi-access = free }}
- {{cite journal | vauthors = Brockmann K, Dumitrescu AM, Best TT, Hanefeld F, Refetoff S | title = X-linked paroxysmal dyskinesia and severe global retardation caused by defective MCT8 gene | journal = Journal of Neurology | volume = 252 | issue = 6 | pages = 663–666 | date = Jun 2005 | pmid = 15834651 | doi = 10.1007/s00415-005-0713-3 | s2cid = 31994320 }}
- {{cite journal | vauthors = Friesema EC, Kuiper GG, Jansen J, Visser TJ, Kester MH | title = Thyroid hormone transport by the human monocarboxylate transporter 8 and its rate-limiting role in intracellular metabolism | journal = Molecular Endocrinology | location = Baltimore, Md. | volume = 20 | issue = 11 | pages = 2761–2772 | date = Nov 2006 | pmid = 16887882 | doi = 10.1210/me.2005-0256 | doi-access = free }}
- {{cite journal | vauthors = Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M | title = Global, in vivo, and site-specific phosphorylation dynamics in signaling networks | journal = Cell | volume = 127 | issue = 3 | pages = 635–648 | date = Nov 2006 | pmid = 17081983 | doi = 10.1016/j.cell.2006.09.026 | s2cid = 7827573 | doi-access = free }}
- {{cite journal | vauthors = Jansen J, Friesema EC, Kester MH, Milici C, Reeser M, Grüters A, Barrett TG, Mancilla EE, Svensson J, Wemeau JL, Busi da Silva Canalli MH, Lundgren J, McEntagart ME, Hopper N, Arts WF, Visser TJ | title = Functional analysis of monocarboxylate transporter 8 mutations identified in patients with X-linked psychomotor retardation and elevated serum triiodothyronine | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 92 | issue = 6 | pages = 2378–2381 | date = Jun 2007 | pmid = 17356046 | doi = 10.1210/jc.2006-2570 | doi-access = free }}
{{refend}}
{{Thyroid hormone metabolism enzymes and transporters}}
{{Membrane transport proteins}}
Category:Solute carrier family