Huntingtin
From Proteopedia
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==Huntingtin protein== | ==Huntingtin protein== | ||
<StructureSection load='2ld0' size='340' side='right' caption='NMR solution structure of the N-terminal domain of huntingtin (htt17) in 50 % TFE' scene=''> | <StructureSection load='2ld0' size='340' side='right' caption='NMR solution structure of the N-terminal domain of huntingtin (htt17) in 50 % TFE' scene=''> | ||
| - | Huntingtin (HTT) is a large (350 kDa) protein essential for embryonic development and is involved in a variety of cellular functions, such as vesicular transport, endocytosis, transcription regulation and autophagy. Mutation in the associated gene — '''IT15''' — results in an expansion of the '''polyQ''' tract found within the N-terminal region of the perspective protein. Such pathological growth, which surpasses the treshold of 36 glutamine residues, may lead to the development of '''Huntington disease'''. The mutation becomes fully penetrant at ≥40 glutamine residues <ref> DOI 10.1097/00005072-199805000-00001</ref>. Mutant huntingtin (mHTT) is prone to aggregation. Yet, despite its ubiquitous expression, mHTT affects primarily the GABAergic '''medium spiny neurons of striatum''' and to a lesser extent the neurons of cerebral cortex <ref>DOI 10.1016/j.nbd.2015.09.008</ref>. | + | Huntingtin (HTT) is a large (350 kDa) protein essential for embryonic development and is involved in a variety of cellular functions, such as vesicular transport, endocytosis, transcription regulation and autophagy. Mutation in the associated gene — '''IT15''' — results in an expansion of the '''polyQ''' tract found within the N-terminal region of the perspective protein. Such pathological growth, which surpasses the treshold of 36 glutamine residues, may lead to the development of '''Huntington disease''' (HD). The mutation becomes fully penetrant at ≥40 glutamine residues <ref> DOI 10.1097/00005072-199805000-00001</ref>. Mutant huntingtin (mHTT) is prone to aggregation. Yet, despite its ubiquitous expression, mHTT affects primarily the GABAergic '''medium spiny neurons of striatum''' and to a lesser extent the neurons of cerebral cortex <ref>DOI 10.1016/j.nbd.2015.09.008</ref>. |
== Function == | == Function == | ||
| + | Since the discovery of HTT and its relevance to HD, efforts have been made to understand the physiological functions of wild-type huntingtin. However, an integrative understanding of its biological functions is still lacking. | ||
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| + | '''Huntingtin and embryonic development''' | ||
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| + | The crucial role of HTT for embryonic development has been shown using mouse knock-out (KO) models, in which homozygous KO mice die at day 8.5 <ref>DOI 10.1038/ng1095-155</ref> | ||
Revision as of 13:16, 18 April 2020
Huntingtin protein
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References
- ↑ Vonsattel JP, DiFiglia M. Huntington disease. J Neuropathol Exp Neurol. 1998 May;57(5):369-84. doi:, 10.1097/00005072-199805000-00001. PMID:9596408 doi:http://dx.doi.org/10.1097/00005072-199805000-00001
- ↑ Guedes-Dias P, Pinho BR, Soares TR, de Proenca J, Duchen MR, Oliveira JM. Mitochondrial dynamics and quality control in Huntington's disease. Neurobiol Dis. 2016 Jun;90:51-7. doi: 10.1016/j.nbd.2015.09.008. Epub 2015 Sep, 24. PMID:26388396 doi:http://dx.doi.org/10.1016/j.nbd.2015.09.008
- ↑ Zeitlin S, Liu JP, Chapman DL, Papaioannou VE, Efstratiadis A. Increased apoptosis and early embryonic lethality in mice nullizygous for the Huntington's disease gene homologue. Nat Genet. 1995 Oct;11(2):155-63. doi: 10.1038/ng1095-155. PMID:7550343 doi:http://dx.doi.org/10.1038/ng1095-155
