Gene Symbol: htt
Description: huntingtin
Alias: CG9995, DmHtt, Dmel\CG9995, HTT, Htt, dHtt, dhtt, huntingtin, CG9995-PA, CG9995-PB, htt-PA, htt-PB
Species: fruit fly

Top Publications

  1. Li Z, Karlovich C, Fish M, Scott M, Myers R. A putative Drosophila homolog of the Huntington's disease gene. Hum Mol Genet. 1999;8:1807-15 pubmed
    The Huntington's disease (HD) gene encodes a protein, huntingtin, with no known function and no detectable sequence similarity to other proteins in current databases...
  2. Doumanis J, Wada K, Kino Y, Moore A, Nukina N. RNAi screening in Drosophila cells identifies new modifiers of mutant huntingtin aggregation. PLoS ONE. 2009;4:e7275 pubmed publisher
    ..screen for modifiers of aggregate formation in Drosophila larval CNS-derived cells expressing mutant human Huntingtin exon 1 fused to EGFP with an expanded polyglutamine repeat (62Q)...
  3. Wu C, Schulte J, Sepp K, Littleton J, Hong P. Automatic robust neurite detection and morphological analysis of neuronal cell cultures in high-content screening. Neuroinformatics. 2010;8:83-100 pubmed publisher
  4. Godin J, Colombo K, Molina Calavita M, Keryer G, Zala D, Charrin B, et al. Huntingtin is required for mitotic spindle orientation and mammalian neurogenesis. Neuron. 2010;67:392-406 pubmed publisher
    b>Huntingtin is the protein mutated in Huntington's disease, a devastating neurodegenerative disorder. We demonstrate here that huntingtin is essential to control mitosis. Huntingtin is localized at spindle poles during mitosis...
  5. Zhang S, Feany M, Saraswati S, Littleton J, Perrimon N. Inactivation of Drosophila Huntingtin affects long-term adult functioning and the pathogenesis of a Huntington's disease model. Dis Model Mech. 2009;2:247-66 pubmed publisher
    A polyglutamine expansion in the huntingtin (HTT) gene causes neurodegeneration in Huntington's disease (HD), but the in vivo function of the native protein (Htt) is largely unknown...
  6. Power D, Srinivasan S, Gunawardena S. In-vivo evidence for the disruption of Rab11 vesicle transport by loss of huntingtin. Neuroreport. 2012;23:970-7 pubmed publisher
    ..Although a role for the Huntington's disease protein huntingtin (HTT) has been reported in axonal transport, it is unclear whether HTT affects the transport of all vesicles or ..
  7. Tamura T, Sone M, Yamashita M, Wanker E, Okazawa H. Glial cell lineage expression of mutant ataxin-1 and huntingtin induces developmental and late-onset neuronal pathologies in Drosophila models. PLoS ONE. 2009;4:e4262 pubmed publisher
    ..We newly generated Drosophila models expressing human mutant huntingtin (hHtt103Q) or ataxin-1 (hAtx1-82Q) in the glial cell lineage at different stages of differentiation, and ..
  8. Sepp K, Hong P, Lizarraga S, Liu J, Mejia L, Walsh C, et al. Identification of neural outgrowth genes using genome-wide RNAi. PLoS Genet. 2008;4:e1000111 pubmed publisher
    ..Collectively, our results showed that RNAi phenotypes in primary neural culture can parallel in vivo phenotypes, and the screening technique can be used to identify many new genes that have important functions in the nervous system. ..
  9. Schulte J, Sepp K, Wu C, Hong P, Littleton J. High-content chemical and RNAi screens for suppressors of neurotoxicity in a Huntington's disease model. PLoS ONE. 2011;6:e23841 pubmed publisher
    ..we conducted high-content small molecule and RNAi suppressor screens using a Drosophila primary neural culture Huntingtin model...

More Information


  1. Gunawardena S, Her L, Brusch R, Laymon R, Niesman I, Gordesky Gold B, et al. Disruption of axonal transport by loss of huntingtin or expression of pathogenic polyQ proteins in Drosophila. Neuron. 2003;40:25-40 pubmed
    ..Reduction of Drosophila huntingtin and expression of proteins containing pathogenic polyQ repeats disrupt axonal transport...
  2. Mugat B, Parmentier M, Bonneaud N, Chan H, Maschat F. Protective role of Engrailed in a Drosophila model of Huntington's disease. Hum Mol Genet. 2008;17:3601-16 pubmed publisher
    Huntington's disease (HD) is caused by the expansion of the polyglutamine (polyQ) tract in the human Huntingtin (hHtt) protein (polyQ-hHtt)...
  3. Berger Z, Davies J, Luo S, Pasco M, Majoul I, O Kane C, et al. Deleterious and protective properties of an aggregate-prone protein with a polyalanine expansion. Hum Mol Genet. 2006;15:453-65 pubmed
    ..Thus, overexpression of an aggregate-prone protein without any normal functions can result in both pathogenic and protective effects in cell culture and in vivo. ..
  4. Shiraishi R, Tamura T, Sone M, Okazawa H. Systematic analysis of fly models with multiple drivers reveals different effects of ataxin-1 and huntingtin in neuron subtype-specific expression. PLoS ONE. 2014;9:e116567 pubmed publisher
    ..We induced expression of the normal and mutant forms of full-length Ataxin-1 and Huntingtin exon 1 in cholinergic, dopaminergic, and motor neurons, and glial cells using cell type-specific drivers...
  5. Liévens J, Rival T, Iché M, Chneiweiss H, Birman S. Expanded polyglutamine peptides disrupt EGF receptor signaling and glutamate transporter expression in Drosophila. Hum Mol Genet. 2005;14:713-24 pubmed
    ..heritable neurodegenerative disorder caused by expansion of a polyglutamine (polyQ) sequence in the protein huntingtin (Htt)...
  6. Gonzales E, Yin J. Drosophila Models of Huntington's Disease exhibit sleep abnormalities. PLoS Curr. 2010;2: pubmed publisher
    ..We show that sleep fragmentation is shared among Drosophila transgenic models that express mutant forms of huntingtin (mHtt), and flies with RNAi-mediated knockdown of the endogenous gene (dhtt)...
  7. Gonzales E, Tanenhaus A, Zhang J, Chaffee R, Yin J. Early-onset sleep defects in Drosophila models of Huntington's disease reflect alterations of PKA/CREB signaling. Hum Mol Genet. 2016;25:837-52 pubmed publisher
    ..Whether sleep and activity abnormalities are primary molecular disruptions of mutant Huntingtin (mutHtt) expression or result from neurodegeneration is unclear...
  8. Underwood B, Imarisio S, Fleming A, Rose C, Krishna G, Heard P, et al. Antioxidants can inhibit basal autophagy and enhance neurodegeneration in models of polyglutamine disease. Hum Mol Genet. 2010;19:3413-29 pubmed publisher
    ..Thus, the potential benefits in neurodegenerative diseases of some classes of antioxidants may be compromised by their autophagy-blocking properties. ..
  9. Fortini M, Skupski M, Boguski M, Hariharan I. A survey of human disease gene counterparts in the Drosophila genome. J Cell Biol. 2000;150:F23-30 pubmed
  10. McLear J, Lebrecht D, Messer A, Wolfgang W. Combinational approach of intrabody with enhanced Hsp70 expression addresses multiple pathologies in a fly model of Huntington's disease. FASEB J. 2008;22:2003-11 pubmed publisher
    ..Furthermore, Hsp70 treatment alone did not block aggregation of mutant huntingtin, a process slowed by intrabody...
  11. Ochaba J, Lukacsovich T, Csikos G, Zheng S, Margulis J, Salazar L, et al. Potential function for the Huntingtin protein as a scaffold for selective autophagy. Proc Natl Acad Sci U S A. 2014;111:16889-94 pubmed publisher
    Although dominant gain-of-function triplet repeat expansions in the Huntingtin (HTT) gene are the underlying cause of Huntington disease (HD), understanding the normal functions of nonmutant HTT protein has remained a challenge...
  12. Freeman A, Syed S, Sanyal S. Modeling the genetic basis for human sleep disorders in Drosophila. Commun Integr Biol. 2013;6:e22733 pubmed publisher
    ..These methodologies should favorably impact not only a mechanistic understanding of sleep, but also future pharmacological intervention strategies to manage and treat sleep disorders in humans. ..
  13. O Rourke J, Gareau J, Ochaba J, Song W, Rasko T, Reverter D, et al. SUMO-2 and PIAS1 modulate insoluble mutant huntingtin protein accumulation. Cell Rep. 2013;4:362-75 pubmed publisher
    A key feature in Huntington disease (HD) is the accumulation of mutant Huntingtin (HTT) protein, which may be regulated by posttranslational modifications...
  14. Wishart T, Rooney T, Lamont D, Wright A, Morton A, Jackson M, et al. Combining comparative proteomics and molecular genetics uncovers regulators of synaptic and axonal stability and degeneration in vivo. PLoS Genet. 2012;8:e1002936 pubmed publisher
    ..We propose that the proteins and functional pathways identified in the current study represent attractive targets for developing therapeutics aimed at modulating synaptic and axonal stability and neurodegeneration in vivo. ..
  15. Kazemi Esfarjani P, Benzer S. Suppression of polyglutamine toxicity by a Drosophila homolog of myeloid leukemia factor 1. Hum Mol Genet. 2002;11:2657-72 pubmed
  16. Rui Y, Xu Z, Patel B, Chen Z, Chen D, Tito A, et al. Huntingtin functions as a scaffold for selective macroautophagy. Nat Cell Biol. 2015;17:262-75 pubmed publisher
    ..Here, we demonstrate that Huntingtin, the Huntington disease gene product, functions as a scaffold protein for selective macroautophagy but it is ..
  17. Pearce M, Spartz E, Hong W, Luo L, Kopito R. Prion-like transmission of neuronal huntingtin aggregates to phagocytic glia in the Drosophila brain. Nat Commun. 2015;6:6768 pubmed publisher
    ..have established a Drosophila model to investigate the role of phagocytic glia in clearance of neuronal mutant huntingtin (Htt) aggregates associated with Huntington disease...
  18. Menzies F, Hourez R, Imarisio S, Raspe M, Sadiq O, Chandraratna D, et al. Puromycin-sensitive aminopeptidase protects against aggregation-prone proteins via autophagy. Hum Mol Genet. 2010;19:4573-86 pubmed publisher
    ..and mouse muscles, PSA inhibition or knockdown increased aggregate content and toxicity of polyQ-expanded huntingtin exon 1. Conversely, PSA overexpression decreased aggregate content and toxicity...
  19. Weiss K, Kimura Y, Lee W, Littleton J. Huntingtin aggregation kinetics and their pathological role in a Drosophila Huntington's disease model. Genetics. 2012;190:581-600 pubmed publisher
    Huntington's disease is a neurodegenerative disorder resulting from expansion of a polyglutamine tract in the Huntingtin protein...
  20. Godin J, Poizat G, Hickey M, Maschat F, Humbert S. Mutant huntingtin-impaired degradation of beta-catenin causes neurotoxicity in Huntington's disease. EMBO J. 2010;29:2433-45 pubmed publisher
    ..We report here a new pathological mechanism by which mutant huntingtin specifically interferes with the degradation of beta-catenin...
  21. Zhang N, Li B, Al Ramahi I, Cong X, Held J, Kim E, et al. Inhibition of lipid signaling enzyme diacylglycerol kinase epsilon attenuates mutant huntingtin toxicity. J Biol Chem. 2012;287:21204-13 pubmed publisher
    ..HD) is a dominantly inherited neurodegenerative disease caused by a polyglutamine expansion in the protein huntingtin (Htt). Striatal and cortical neuronal loss are prominent features of this disease...
  22. Sang T, Li C, Liu W, Rodriguez A, Abrams J, Zipursky S, et al. Inactivation of Drosophila Apaf-1 related killer suppresses formation of polyglutamine aggregates and blocks polyglutamine pathogenesis. Hum Mol Genet. 2005;14:357-72 pubmed
    Huntington's disease (HD) is caused by expansion of a polyglutamine tract near the N-terminal of huntingtin. Mutant huntingtin forms aggregates in striatum and cortex, where extensive cell death occurs...
  23. White J, Anderson E, Zimmerman K, Zheng K, Rouhani R, Gunawardena S. Huntingtin differentially regulates the axonal transport of a sub-set of Rab-containing vesicles in vivo. Hum Mol Genet. 2015;24:7182-95 pubmed publisher
    Loss of huntingtin (HTT), the Huntington's disease (HD) protein, was previously shown to cause axonal transport defects...
  24. El Daher M, Hangen E, Bruyère J, Poizat G, Al Ramahi I, Pardo R, et al. Huntingtin proteolysis releases non-polyQ fragments that cause toxicity through dynamin 1 dysregulation. EMBO J. 2015;34:2255-71 pubmed publisher
    Cleavage of mutant huntingtin (HTT) is an essential process in Huntington's disease (HD), an inherited neurodegenerative disorder...
  25. Steinert J, Campesan S, Richards P, Kyriacou C, Forsythe I, Giorgini F. Rab11 rescues synaptic dysfunction and behavioural deficits in a Drosophila model of Huntington's disease. Hum Mol Genet. 2012;21:2912-22 pubmed publisher
    ..The polyglutamine expansion in the huntingtin (htt) protein that underlies this disorder leads to perturbations in many cellular pathways, including the ..
  26. Zala D, Hinckelmann M, Saudou F. Huntingtin's function in axonal transport is conserved in Drosophila melanogaster. PLoS ONE. 2013;8:e60162 pubmed publisher
    ..inherited neurodegenerative disorder caused by an abnormal polyglutamine expansion in the N-terminal part of the huntingtin (HTT) protein...
  27. Demontis F, Dahmann C. Characterization of the Drosophila ortholog of the human Usher Syndrome type 1G protein sans. PLoS ONE. 2009;4:e4753 pubmed publisher
    ..Our work is consistent with an evolutionary conserved function of Sans in vesicle trafficking. Furthermore it provides a significant basis for further understanding of the role of this Usher syndrome ortholog in development and disease. ..
  28. Dietz K, Di Stefano L, Maher R, Zhu H, MacDonald M, Gusella J, et al. The Drosophila Huntington's disease gene ortholog dhtt influences chromatin regulation during development. Hum Mol Genet. 2015;24:330-45 pubmed publisher an autosomal dominant neurodegenerative disorder caused by a CAG expansion mutation in HTT, the gene encoding huntingtin. Evidence from both human genotype-phenotype relationships and mouse model systems suggests that the mutation ..
  29. Chondrogianni N, Sakellari M, Lefaki M, Papaevgeniou N, Gonos E. Proteasome activation delays aging in vitro and in vivo. Free Radic Biol Med. 2014;71:303-20 pubmed publisher
    ..This review article reports on the means of function of these proteasome activators and how they regulate aging in various species. ..
  30. Kuo Y, Ren S, Lao U, Edgar B, Wang T. Suppression of polyglutamine protein toxicity by co-expression of a heat-shock protein 40 and a heat-shock protein 110. Cell Death Dis. 2013;4:e833 pubmed publisher
    ..Our data provide a functional link between HSP40 and HSP110 in suppressing the cytotoxicity of aggregation-prone proteins, and suggest that HSP40 and HSP110 function together in protein homeostasis control. ..
  31. Berger Z, Ttofi E, Michel C, Pasco M, Tenant S, Rubinsztein D, et al. Lithium rescues toxicity of aggregate-prone proteins in Drosophila by perturbing Wnt pathway. Hum Mol Genet. 2005;14:3003-11 pubmed
  32. Scappini E, Koh T, Martin N, O Bryan J. Intersectin enhances huntingtin aggregation and neurodegeneration through activation of c-Jun-NH2-terminal kinase. Hum Mol Genet. 2007;16:1862-71 pubmed
    ..a progressive neurodegenerative disease arising from expansion of a polyglutamine (polyQ) tract in the protein huntingtin (Htt) resulting in aggregation of mutant Htt into nuclear and/or cytosolic inclusions in neurons...
  33. Miller J, Yates B, Al Ramahi I, Berman A, Sanhueza M, Kim E, et al. A genome-scale RNA-interference screen identifies RRAS signaling as a pathologic feature of Huntington's disease. PLoS Genet. 2012;8:e1003042 pubmed publisher
    A genome-scale RNAi screen was performed in a mammalian cell-based assay to identify modifiers of mutant huntingtin toxicity...
  34. Kumar A, Singh P, Parihar R, Dwivedi V, Lakhotia S, Ganesh S. Decreased O-linked GlcNAcylation protects from cytotoxicity mediated by huntingtin exon1 protein fragment. J Biol Chem. 2014;289:13543-53 pubmed publisher that decreasing O-GlcNAcylation enhances the viability of neuronal cells expressing polyglutamine-expanded huntingtin exon 1 protein fragment (mHtt)...
  35. Miller J, Holcomb J, Al Ramahi I, de Haro M, Gafni J, Zhang N, et al. Matrix metalloproteinases are modifiers of huntingtin proteolysis and toxicity in Huntington's disease. Neuron. 2010;67:199-212 pubmed publisher
    Proteolytic cleavage of huntingtin (Htt) is known to be a key event in the pathogenesis of Huntington's disease (HD). Our understanding of proteolytic processing of Htt has thus far focused on the protease families-caspases and calpains...
  36. Babcock D, Ganetzky B. Transcellular spreading of huntingtin aggregates in the Drosophila brain. Proc Natl Acad Sci U S A. 2015;112:E5427-33 pubmed publisher
    ..Here we use a polyglutamine-expanded form of human huntingtin (Htt) with a fluorescent tag to monitor the spreading of aggregates in the Drosophila brain in a model of ..
  37. Luthi Carter R, Taylor D, Pallos J, Lambert E, Amore A, Parker A, et al. SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis. Proc Natl Acad Sci U S A. 2010;107:7927-32 pubmed publisher
    ..Whereas mutant huntingtin fragments increased sterols in neuronal cells, SIRT2 inhibition reduced sterol levels via decreased nuclear ..
  38. Hill E. Cellular inheritance. PLoS Biol. 2006;4:e446 pubmed publisher
  39. Lo Sardo V, Zuccato C, Gaudenzi G, Vitali B, Ramos C, Tartari M, et al. An evolutionary recent neuroepithelial cell adhesion function of huntingtin implicates ADAM10-Ncadherin. Nat Neurosci. 2012;15:713-21 pubmed publisher
    The Huntington's disease gene product, huntingtin, is indispensable for neural tube formation, but its role is obscure...
  40. Bulgari D, Deitcher D, Levitan E. Loss of Huntingtin stimulates capture of retrograde dense-core vesicles to increase synaptic neuropeptide stores. Eur J Cell Biol. 2017;96:402-406 pubmed publisher
    The Huntington's disease protein Huntingtin (Htt) regulates axonal transport of dense-core vesicles (DCVs) containing neurotrophins and neuropeptides...
  41. Fujikake N, Nagai Y, Popiel H, Okamoto Y, Yamaguchi M, Toda T. Heat shock transcription factor 1-activating compounds suppress polyglutamine-induced neurodegeneration through induction of multiple molecular chaperones. J Biol Chem. 2008;283:26188-97 pubmed publisher
    ..Our study indicates that induction of multiple molecular chaperones by 17-AAG treatment is a promising therapeutic approach for a wide range of polyQ diseases and possibly other neurodegenerative diseases. ..
  42. Zheng Q, Joinnides M. Hunting for the function of Huntingtin. Dis Model Mech. 2009;2:199-200 pubmed publisher
  43. Feany M, La Spada A. Polyglutamines stop traffic: axonal transport as a common target in neurodegenerative diseases. Neuron. 2003;40:1-2 pubmed
    ..Gunawardena et al. show that normal levels of huntingtin are required for proper axonal transport in Drosophila...
  44. Takano H, Gusella J. The predominantly HEAT-like motif structure of huntingtin and its association and coincident nuclear entry with dorsal, an NF-kB/Rel/dorsal family transcription factor. BMC Neurosci. 2002;3:15 pubmed
    Huntington's disease (HD) pathogenesis is due to an expanded polyglutamine tract in huntingtin, but the specificity of neuronal loss compared with other polyglutamine disorders also implies a role for the protein's unknown inherent ..
  45. Grima J, Daigle J, Arbez N, Cunningham K, Zhang K, Ochaba J, et al. Mutant Huntingtin Disrupts the Nuclear Pore Complex. Neuron. 2017;94:93-107.e6 pubmed publisher
    Huntington's disease (HD) is caused by an expanded CAG repeat in the Huntingtin (HTT) gene. The mechanism(s) by which mutant HTT (mHTT) causes disease is unclear...