Huntingtin: here, there, everywhere!

Huntingtin is the protein mutated in Huntington disease, a dominant inherited neurodegenerative disorder. Huntingtin is ubiquitously expressed throughout the body, however its role outside the central nervous system has been overlooked. This review focuses on the peripheral distribution of huntingtin. It also highlights that huntingtin has central cellular functions, the importance of which may extend beyond the nervous system. Because of the breadth of huntingtin expression and functions, mutant huntingtin undoubtedly causes peripheral disturbances and may be involved in other non neuronal pathologies.

[1]  S. Humbert,et al.  Huntingtin Acts Non Cell-Autonomously on Hippocampal Neurogenesis and Controls Anxiety-Related Behaviors in Adult Mouse , 2013, PloS one.

[2]  K. Deisseroth,et al.  CLARITY for mapping the nervous system , 2013, Nature Methods.

[3]  S. Humbert,et al.  Huntingtin Mediates Anxiety/Depression-Related Behaviors and Hippocampal Neurogenesis , 2013, The Journal of Neuroscience.

[4]  F. Saudou,et al.  Mutant Huntingtin Alters Retrograde Transport of TrkB Receptors in Striatal Dendrites , 2013, The Journal of Neuroscience.

[5]  S. Tezenas du Montcel,et al.  The Huntington disease protein accelerates breast tumour development and metastasis through ErbB2/HER2 signalling , 2013, EMBO molecular medicine.

[6]  R. Atwal,et al.  Identification of a Karyopherin β1/β2 Proline-Tyrosine Nuclear Localization Signal in Huntingtin Protein* , 2012, The Journal of Biological Chemistry.

[7]  Jan Sundquist,et al.  Cancer incidence in patients with polyglutamine diseases: a population-based study in Sweden. , 2012, The Lancet. Oncology.

[8]  J. Gusella,et al.  An evolutionary recent neuroepithelial cell adhesion function of huntingtin implicates ADAM10-Ncadherin , 2012, Nature Neuroscience.

[9]  R. Ferrante,et al.  Ciliogenesis is regulated by a huntingtin-HAP1-PCM1 pathway and is altered in Huntington disease. , 2011, The Journal of clinical investigation.

[10]  B. Christie,et al.  Altered adult hippocampal neurogenesis in the YAC128 transgenic mouse model of Huntington disease , 2011, Neurobiology of Disease.

[11]  Yohanns Bellaiche,et al.  Huntingtin Is Required for Mitotic Spindle Orientation and Mammalian Neurogenesis , 2010, Neuron.

[12]  G. Bates,et al.  Formation of Polyglutamine Inclusions in a Wide Range of Non-CNS Tissues in the HdhQ150 Knock-In Mouse Model of Huntington's Disease , 2009, PloS one.

[13]  V. Silani,et al.  Huntington's disease: The current state of research with peripheral tissues , 2009, Experimental Neurology.

[14]  P. Brundin,et al.  Beyond the brain: widespread pathology in Huntington's disease , 2009, The Lancet Neurology.

[15]  N. Perrimon,et al.  Inactivation of Drosophila Huntingtin affects long-term adult functioning and the pathogenesis of a Huntington’s disease model , 2009, Disease Models & Mechanisms.

[16]  F. Pontén,et al.  The Human Protein Atlas—a tool for pathology , 2008, The Journal of pathology.

[17]  Z. Qin,et al.  A function of huntingtin in guanine nucleotide exchange on Rab11 , 2008, Neuroreport.

[18]  S. Humbert,et al.  Huntingtin phosphorylation acts as a molecular switch for anterograde/retrograde transport in neurons , 2008, The EMBO journal.

[19]  M. Hayden,et al.  A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease , 2008, The Journal of experimental medicine.

[20]  Carlos Cepeda,et al.  Full-Length Human Mutant Huntingtin with a Stable Polyglutamine Repeat Can Elicit Progressive and Selective Neuropathogenesis in BACHD Mice , 2008, The Journal of Neuroscience.

[21]  R. Atwal,et al.  Nucleocytoplasmic trafficking and transcription effects of huntingtin in Huntington's disease , 2007, Progress in Neurobiology.

[22]  R. Richards,et al.  Huntingtin-deficient zebrafish exhibit defects in iron utilization and development. , 2007, Human molecular genetics.

[23]  S. Humbert,et al.  Phosphorylation of Huntingtin by Cyclin-Dependent Kinase 5 Is Induced by DNA Damage and Regulates Wild-Type and Mutant Huntingtin Toxicity in Neurons , 2007, The Journal of Neuroscience.

[24]  J. Caviston,et al.  Huntingtin facilitates dynein/dynactin-mediated vesicle transport , 2007, Proceedings of the National Academy of Sciences.

[25]  M. Hayden,et al.  Testicular degeneration in Huntington disease , 2007, Neurobiology of Disease.

[26]  R. Myers,et al.  Wild-type huntingtin participates in protein trafficking between the Golgi and the extracellular space. , 2007, Human molecular genetics.

[27]  K. Hoyt,et al.  Cardiac dysfunction in the R6/2 mouse model of Huntington’s disease , 2007, Neurobiology of Disease.

[28]  M. Russo,et al.  Increased apoptosis, huntingtin inclusions and altered differentiation in muscle cell cultures from Huntington's disease subjects , 2006, Cell Death and Differentiation.

[29]  A. Shevchenko,et al.  Huntingtin–HAP40 complex is a novel Rab5 effector that regulates early endosome motility and is up-regulated in Huntington's disease , 2006, The Journal of cell biology.

[30]  Xiao-Jiang Li,et al.  Interaction of Huntingtin-associated Protein-1 with Kinesin Light Chain , 2006, Journal of Biological Chemistry.

[31]  M. Hayden,et al.  Wild‐type huntingtin protects neurons from excitotoxicity , 2006, Journal of neurochemistry.

[32]  F. Squitieri,et al.  Huntingtin fragmentation and increased caspase 3, 8 and 9 activities in lymphoblasts with heterozygous and homozygous Huntington's disease mutation , 2006, Mechanisms of Ageing and Development.

[33]  B. Harper Huntington Disease , 2005, Journal of the Royal Society of Medicine.

[34]  S. Snyder,et al.  p53 Mediates Cellular Dysfunction and Behavioral Abnormalities in Huntington’s Disease , 2005, Neuron.

[35]  Erik Renström,et al.  The R6/2 transgenic mouse model of Huntington's disease develops diabetes due to deficient beta-cell mass and exocytosis. , 2005, Human molecular genetics.

[36]  Fabrice P Cordelières,et al.  Huntingtin Controls Neurotrophic Support and Survival of Neurons by Enhancing BDNF Vesicular Transport along Microtubules , 2004, Cell.

[37]  Richard G. Brusch,et al.  Disruption of Axonal Transport by Loss of Huntingtin or Expression of Pathogenic PolyQ Proteins in Drosophila , 2003, Neuron.

[38]  Andrea Crotti,et al.  Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes , 2003, Nature Genetics.

[39]  Erich E Wanker,et al.  The hunt for huntingtin function: interaction partners tell many different stories. , 2003, Trends in biochemical sciences.

[40]  R. Truant,et al.  Huntingtin contains a highly conserved nuclear export signal. , 2003, Human molecular genetics.

[41]  L. Farrell,et al.  Mutant huntingtin increases nuclear corepressor function and enhances ligand-dependent nuclear hormone receptor activation , 2003, Molecular and Cellular Neuroscience.

[42]  J. Gusella,et al.  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 , 2002, BMC Neuroscience.

[43]  M. Chesselet,et al.  Comparison of huntingtin proteolytic fragments in human lymphoblast cell lines and human brain , 2002, Journal of neurochemistry.

[44]  A. Dale,et al.  Regional and progressive thinning of the cortical ribbon in Huntington’s disease , 2002, Neurology.

[45]  He Li,et al.  Interaction of Huntington Disease Protein with Transcriptional Activator Sp1 , 2002, Molecular and Cellular Biology.

[46]  J. Nevins,et al.  Huntingtin Is Present in the Nucleus, Interacts with the Transcriptional Corepressor C-terminal Binding Protein, and Represses Transcription* , 2002, The Journal of Biological Chemistry.

[47]  Pascal Kahlem,et al.  Perinuclear localization of huntingtin as a consequence of its binding to microtubules through an interaction with beta-tubulin: relevance to Huntington's disease. , 2002, Journal of cell science.

[48]  David G. Drubin,et al.  The actin-binding protein Hip1R associates with clathrin during early stages of endocytosis and promotes clathrin assembly in vitro , 2001, The Journal of cell biology.

[49]  H. Lehrach,et al.  The huntingtin interacting protein HIP1 is a clathrin and alpha-adaptin-binding protein involved in receptor-mediated endocytosis. , 2001, Human molecular genetics.

[50]  R. Myers,et al.  Juvenile onset Huntington's disease--clinical and research perspectives. , 2001, Mental retardation and developmental disabilities research reviews.

[51]  Blair R. Leavitt,et al.  Loss of Huntingtin-Mediated BDNF Gene Transcription in Huntington's Disease , 2001, Science.

[52]  D. Rigamonti,et al.  Huntingtin's Neuroprotective Activity Occurs via Inhibition of Procaspase-9 Processing* , 2001, The Journal of Biological Chemistry.

[53]  A. Hackam,et al.  Huntingtin Interacting Protein 1 Induces Apoptosis via a Novel Caspase-dependent Death Effector Domain* , 2000, The Journal of Biological Chemistry.

[54]  Michael S. Levine,et al.  Inactivation of Hdh in the brain and testis results in progressive neurodegeneration and sterility in mice , 2000, Nature Genetics.

[55]  D. Housman,et al.  The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[56]  A. Hackam,et al.  Wild-Type Huntingtin Protects from Apoptosis Upstream of Caspase-3 , 2000, The Journal of Neuroscience.

[57]  M. Hayden,et al.  Huntingtin is required for normal hematopoiesis. , 2000, Human molecular genetics.

[58]  S. Snyder,et al.  Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization , 1999, Nature Medicine.

[59]  K Fenger,et al.  Significantly lower incidence of cancer among patients with Huntington disease , 1999, Cancer.

[60]  D. Tagle,et al.  Transgenic mice expressing mutated full-length HD cDNA: a paradigm for locomotor changes and selective neuronal loss in Huntington's disease. , 1999, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[61]  S. W. Davies,et al.  Formation of polyglutamine inclusions in non-CNS tissue. , 1999, Human molecular genetics.

[62]  M. MacDonald,et al.  Huntingtin interacts with a family of WW domain proteins. , 1998, Human molecular genetics.

[63]  S. Zeitlin,et al.  Mouse mutant embryos lacking huntingtin are rescued from lethality by wild-type extraembryonic tissues. , 1998, Development.

[64]  S. Hersch,et al.  Interaction of Huntingtin-Associated Protein with Dynactin P150Glued , 1998, The Journal of Neuroscience.

[65]  G. Pearlson,et al.  Frontal lobe volume in patients with Huntington's disease , 1998, Neurology.

[66]  I. Kanazawa,et al.  HIP1, a human homologue of S. cerevisiae Sla2p, interacts with membrane-associated huntingtin in the brain , 1997, Nature Genetics.

[67]  H. Lehrach,et al.  HIP-I: a huntingtin interacting protein isolated by the yeast two-hybrid system. , 1997, Human molecular genetics.

[68]  D. Zamanillo,et al.  Identification of a long huntingtin mRNA transcript in mouse brain , 1996, Brain Research.

[69]  J. D. den Dunnen,et al.  Subcellular localization of the Huntington's disease gene product in cell lines by immunofluorescence and biochemical subcellular fractionation. , 1996, Human molecular genetics.

[70]  P S Harper,et al.  Partial characterisation of murine huntingtin and apparent variations in the subcellular localisation of huntingtin in human, mouse and rat brain. , 1996, Human molecular genetics.

[71]  S. Snyder,et al.  A huntingtin-associated protein enriched in brain with implications for pathology , 1995, Nature.

[72]  M. Perutz,et al.  Glutamine Repeats as Polar Zippers: Their Role in Inherited Neurodegenerative Disease , 1995, Molecular medicine.

[73]  Virginia E. Papaioannou,et al.  Increased apoptosis and early embryonic lethality in mice nullizygous for the Huntington's disease gene homologue , 1995, Nature Genetics.

[74]  S. Hersch,et al.  Identification and localization of huntingtin in brain and human lymphoblastoid cell lines with anti-fusion protein antibodies. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[75]  C. Ross,et al.  Expression of the Huntington's disease (IT15) protein product in HD patients. , 1995, Human molecular genetics.

[76]  A. Joyner,et al.  Inactivation of the mouse Huntington's disease gene homolog Hdh. , 1995, Science.

[77]  O. Riess,et al.  Expression of the Huntington disease gene in rodents: cloning the rat homologue and evidence for downregulation in non-neuronal tissues during development. , 1995, Human molecular genetics.

[78]  S. Floresco,et al.  Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes , 1995, Cell.

[79]  M. Dragunow,et al.  In situ evidence for DNA fragmentation in Huntington's disease striatum and Alzheimer's disease temporal lobes , 1995, Neuroreport.

[80]  Christopher A Ross,et al.  Widespread expression of Huntington's disease gene (IT15) protein product , 1995, Neuron.

[81]  E. Hirsch,et al.  Cellular localization of the Huntington's disease protein and discrimination of the normal and mutated form , 1995, Nature Genetics.

[82]  R. Carraway,et al.  Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons , 1995, Neuron.

[83]  S. Rusconi,et al.  Transcriptional activation modulated by homopolymeric glutamine and proline stretches. , 1994, Science.

[84]  R. Roos,et al.  Characterization and localization of the Huntington disease gene product. , 1993, Human molecular genetics.

[85]  S. Folstein,et al.  Huntington's disease gene (IT15) is widely expressed in human and rat tissues , 1993, Neuron.

[86]  R. Albin,et al.  Widespread expression of the human and rat Huntington's disease gene in brain and nonneural tissues , 1993, Nature Genetics.

[87]  Manish S. Shah,et al.  A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes , 1993, Cell.