Abstract
Huntington’s disease (HD), with its writhing dancelike movements (chorea) and cardinal loss of neurons in the striatum (1), is the result of an unstable expanded CAG trinucleotide repeat that lengthens a variable glutamine tract in a novel protein called huntingtin (HD) (2). HD shares elements of a common pathogenic mechanism with at least seven other inherited neurodegenerative diseases, including spinobulbar muscular atrophy (SBMA) (3), dentatorubral-pallidoluysian atrophy (DRPLA/Haw River syndrome) (4–6), and several spinocerebellar ataxias (SCA1, SCA2, SCA3/MJD, SCA6 and SCA7) (7–14) (Fig. 1). Expanded glutamine segments in otherwise unrelated proteins cause specific neuronal cell loss in each case, suggesting unique protein context-dependent modulation of some intrinsic toxic property of polyglutamine (15–17). In this view, some feature of huntingtin produces HD pathology by presenting the embedded toxic glutamine tract to cells in a manner that culminates in a graded loss of striatal neurons. One molecular possibility is a glutamine-induced conformational change that alters huntingtin’s association with its normal or abnormal protein partners (18,19).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Folstein, S. (1989) Huntington’s Disease: A Disorder of Families. The Johns Hopkins Press, Baltimore, pp. 13–64.
Huntington’s Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 72, 971–983.
LaSpada, A. R., Wilson, E. M., Lubahn, D. B., Harding, A. E., and Fishbeck, H. (1991) Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 352, 77–79.
Koide, R., Ikeuchi, T., Onodera, O., Tanaka, H., Igarashi, S., Endo, K., et al. (1994) Unstable expansion of CAG repeat in hereditary dentatorubralpallidoluysian atrophy (DRPLA). Nat. Genet. 6, 9–13.
Nagafuchi, S., Yanagisawa, H., Sato, K., Shirayama, T., Ohsaki, E., Bundo, M., et al. (1994) Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG trinucleotide on chromosome 12p. Nat. Genet. 6, 14–18.
Burke, J. R., Wingfield, M. S., Lewis, K. E., Roses, A. D., Lee, J. E., Hulette, C., et al. (1994) The Haw River Syndrome: dentatorubropallidoluysian atrophy (DRPLA) in an African-American family. Nat. Genet. 7, 521–524.
Zoghbi, H. Y. and Orr, H. T. (1995) Spinocerebellar ataxia type 1. Semin Cell Biol. 6, 29–35.
Imbert, G., Saudou, F., Yvert, G., Devys, D., Trottier, Y., Gamier, J. M., et al. (1996) Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats. Nat. Genet. 14, 285–291.
Pulst, S. M., Nechiporuk, A., Nechiporuk, T., Gispert, S., Chen, X. N., LopesCendes, I., et al. (1996) Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2. Nat. Genet. 14, 269–276.
Sanpei, K., Takano, H., Igarashi, S., Sato, T., Oyake, M., Sasaki, H., et al. (1996) Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT. Nat. Genet. 14, 277–284.
Kawaguchi, Y., Okamoto, T., Taniwaki, M., Aizawa, M., Inoue, M., Katayama, S., et al. (1994) CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat. Genet. 8, 221–228.
Haberhausen, G., Damian, M. S., Leweke, F., and Muller, U. (1995) Spinocerebellar ataxia, type 3 (SCA3) is genetically identical to Machado-Joseph disease (MJD). J. Neurol. Sci. 132, 71–75.
Zhuchenko, O., Bailey, J., Bonnen, P., Ashizawa, T., Stockton, D. W., Amos, C., et al. (1997) Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alphalA-voltage-dependent calcium channel. Nat. Genet. 15, 62–68.
Lindblad, K., Savontaus, M. L., Stevanin, G., Holmberg, M., Digre, K., Zander, C., et al. (1996) An expanded CAG repeat sequence in spinocerebellar ataxia type 7. Genome Res. 6, 965–971.
Ross, C. A. (1995) When more is less, pathogenesis of glutamine repeat neurodegenerative diseases. Neuron 15, 493–496.
Ross, C. A. (1997) Intranuclear neuronal inclusions, a common pathogenic mechanism for glutamine-repeat neurodegenerative diseases? Neuron 19, 1147–1150.
Gusella, J. F., Persichetti, F., and MacDonald, M. E. (1997) The genetic defect causing Huntington’s disease, repeated in other contexts? Mol. Med. 3, 238–246.
Ross, C. A., Becher, M. W., Colomer, V., Engelender, S., Wood, J. D., and Sharp, A. H. (1997) Huntington’s disease and dentatorubral-pallidoluysian atrophy, proteins, pathogenesis and pathology. Brain Pathol. 7, 1003–1016.
Gusella, J. F. and MacDonald, M. E. (1998) Huntingtin, A single bait hooks many species. Curr. Opin. Neurobiol. 8, 425–430.
Choi, D. W. (1988) Glutamate neurotoxicity and diseases of the nervous system. Neuron 1, 623–634.
Albin, R. L. and Greenamyre, J. T. (1992) Alternative excitotoxic hypotheses. Neurology 42, 733–738.
Coyle, J. T. and Puttfarcken, P. (1993) Oxidative stress, glutamate, and neurodegenerative disorders. Science 262, 689–695.
Beal, M. F. (1994) Huntington’s disease, energy and excitotoxicity. Neurobiol. Aging 15, 275–276.
Shulz, J. B., Matthews, R. T., Jenkins, B. G., Ferrante, R. J., Cipolloni, P. B., Kowall, N. W., et al. (1995) Involvement of free radicals in excitotoxicity in vivo. J. Neurochem. 64, 2239–2247.
Nasir, J., Floresco, S. B., O’Kuskey, J. R., Diewert, V. M., Richman, J. M., Zeisler, J., et al. (1995) Targeted disruption of the Huntington’s disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes. Cell 81, 811–823.
Duyao, M. P., Auerbach, A. B., Ryan, A., Persichetti, F., Barnes, G. T., McNeil, S. M., et al. (1995) Inactivation of the mouse Huntington’s disease gene homolog Hdh. Science 269, 407–410.
Zeitlin, S., Liu, J. P., Chapman, D. L., Papaioannou, V. E., and Efstratiadis, A. (1995) Increased apoptosis and early embryonic lethality in mice nullizygous for the Huntington’s disease gene homologue. Nat. Genet. 11, 155–163.
White, J. K., Auerbach, W., Duyao, M. P., Vonsattel, J. P., Gusella, J. F., Joyner, A. L. et al. (1997) Huntingtin is required for neurogenesis and is not impaired by the Huntington’s disease CAG expansion. Nat. Genet. 17, 404–410.
Gusella, J. F., McNeil, S., Persichetti, F., Srinidhi, J., Novelletto, A., Bird, E., et al. (1996) Huntington’s Disease. Cold Spring Harbor Sympos. Quant. Biol. 61, 615–625.
Albin, R. L. (1995) Selective neurodegeneration in Huntington’s disease. Ann. Neurol. 38, 835–836.
Vonsattel, J. P. and DiFiglia, M. (1998) Huntington disease. J. Neuropathol. Exp. Neurol. 57, 369–384.
McNeil, S. M., Novelletto, A., Srinidhi, J., Barnes, G., Kornbluth, I., Altherr, M. R., et al. (1997) Reduced penetrance of the Huntington’s disease mutation. Hum. Mol. Genet. 6, 775–779.
Rubinsztein, D. C., Leggo, J., Coles, R., Almqvist, E., Biancalana, V., Cassiman, J. J., et al. (1996) Phenotypic characterization of individuals with 30–40 CAG repeats in the Huntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36–39 repeats. Am. J. Hum. Genet. 9, 16–22.
MacDonald, M. E., Barnes, G., Srinidhi, J., Duyao, M. P., Ambrose, C. M., Myers, R. H., et al. (1993) Gametic but not somatic instability of CAG repeat length in Huntington’s disease. J. Med. Genet. 30, 982–986.
Penney, J. B., Jr., Vonsattel, J. P., MacDonald, M. E., Gusella, J. F., and Myers, R. H. (1997) CAG repeat number governs the development rate of pathology in Huntington’s disease. Ann. Neurol. 41, 689–692.
Persichetti, F., Srinidhi, J., Kanaley, L., Ge, P., Myers, R. H., D’Arrigo, K., et al. (1994) Huntington’s disease CAG trinucleotide repeats in pathologically confirmed post—mortem brains. Neurobiol. Dis. 1, 159–166.
Ambrose, C. M., Duyao, M. P., Barnes, G., Bates, G. P., Lin, C. S., Srinidhi, J., et al. (1994) Structure and expression of the Huntington’s disease gene, evidence against simple inactivation due to an expanded CAG repeat. Somat. Cell. Mol. Genet. 20, 27–38.
Wexler, N. S., Young, A. B., Tanzi, R. E., Travers, H., Starosta-Rubenstein, S., Penney, J. B., et al. (1987) Homozygotes for Huntington’s disease. Nature 326, 194–197.
Myers, R. H., Leavitt, J., Farrer, L. A., Jagadeesh, J., McFarlane, H., Mark, R. J., et al. (1989) Homozygote for Huntington’s disease. Am. J. Hum. Genet. 45, 615–618.
MacDonald, M. E. and Gusella, J. F. (1996) Huntington’s disease: translating a CAG repeat into a pathogenic mechanism. Curr. Opin. Neurobiol. 6, 638–643.
Jou Y-S. and Myers, R. M. (1995) Evidence from antibody studies that the CAG repeat in the Huntington’s disease gene is expressed in the protein. Hum. Mol. Genet. 4, 465–469.
Ide, K., Nukina, N., Masuda, N., Goto, J., and Kanazawa, I. (1995) Abnormal gene product identified in Huntington’s disease lymphocytes and brain. Biochem. Biophys. Res. Commun. 209, 1119–1125.
Baxendale, S., Abdulla, S., Elgar, G., Buck, D., Berks, M., Micklem, G., et al. (1995) Comparative sequence analysis of the human and pufferfish Huntington’s disease genes. Nat. Genet, 10, 67–76.
Karlovich, C. A., John, R. M., Ramirez, L., Stainier, D. Y. R., and Myers, R. M. (1998) Characterization of the Huntington’s disease (HD) gene homolog in the zebrafish Danio rerio Gene 217, 117–125.
Lin, B., Nasir, J., MacDonald, H., Hutchinson, G., Graham, R. K., Rommens, J. M., et al. (1994) Sequence of the murine Huntington disease gene, evidence for conservation, alternate splicing and polymorphism in a triplet (CCG) repeat. Hum. Mol. Genet. 3, 85–92; erratum: Hum. Mol. Genet. 3, 530 (1994).
Barnes, G. T., Duyao, M. P., Ambrose, C. M., McNeil, S., Persichetti, F., Srinidhi, J., et al. (1994) Mouse Huntington’s disease gene homolog (Hdh) Somat.Cell. Mol. Genet. 20, 87–97.
Schmitt, I., Baechner, D., Megow, D., Henklein, P., Boulter, J., Hameister, H., et al. (1995) Expression of the Huntington disease gene in rodents: cloning the rat homologue and evidence for down regulation in non—neuronal tissues during development. Hum. Mol. Genet. 4, 1173–1182.
Andrade, M. A. and Bork, P. (1995) HEAT repeats in the Huntington’s disease protein. Nat. Genet. 11, 115–116.
Groves, M. R., Hanlon, N., Turowski, P., Hemmings, B. A., and Barford, D. (1999) The structure of the protein phosphatase 2A PR65/A subunit reveals the conformation of its 15 tandemly repeated HEAT motifs. Cell 96, 99–110.
Cingolani, G., Petosa, C., Weis, K., and Muller, C. W. (1999) Structure of importin-beta bound to the IBB domain of importin-alpha. Nature 399, 221–229.
Landschulz, W. H., Johnson, K. S., and McKnight, S. L. (1988) The leucine zipper. A hypothetical structure common to a new class of DNA binding proteins. Science 240, 1759–1764.
Sharp, A. H. and Ross, C. A. (1996) Neurobiology of Huntington’s disease. Neurobiol. Dis. 3, 3–15.
Sharp, A. H., Loev, S. J., Schilling, G., Li, S-H., Li, X-J, Bao, J. et al. (1995) Widespread expression of the Huntington’s disease gene (IT-15) protein product. Neuron 14, 1065–1074.
DiFiglia, M., Sapp, E., Chase, K., Schwarz, C., Meloni, A., Young, C., et al. (1995) Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons. Neuron 14, 1075–1081.
Gutekunst C.-A, Levey AI, Heilman CJ, Whaley WL, Hong Y, Nash NR, et al. (1995) Identification and localization of huntingtin in brain and human lymphoblastoid cell lines with anti-fusion protein antibodies. Proc. Natl. Acad. Sci. USA 92, 8710–8714
Persichetti, F., Carlee, L., Faber, P. W., McNeil, S. M., Ambrose, C. M., Srinidhi, J., et al. (1996). Differential expression of normal and mutant Huntington’s disease gene alleles. Neurobiol. Dis. 3, 183–190.
Ferrante, R. J., Gutekunst, C. A., Persichetti, F., McNeil, S. M., Kowall, N. W., Gusella, J. F., et al. (1997) Heterogeneous topographic and cellular distribution of huntingtin expression in the normal human neostriatum. J. Neurosci. 17, 3052–3063
Velier, J., Kim, M., Schwarz, C., Kim, T. W., Sapp, E., Chase, K., et al. (1998) Wild—type and mutant huntingtins function in vesicle trafficking in the secretory and endocytic pathways. Exp. Neurol. 152, 34–40.
Hoogeveen, A. T., Willemsen, R., Meyer, N., de Rooij, K. E., Roos, R. A., van Ommen, G. J., et al. (1993) Characterization and localization of the Huntington disease gene product. Hum. Mol. Genet. 2, 2069–2073.
De Rooij, K. E., Dorsman, J. C., Smoor, M. A., Den Dunnen, J. T., and Van Ommen, G. J. (1996) Subcellular localization of the Huntington’s disease gene product in cell lines by immunofluorescence and biochemical subcellular fractionation. Hum. Mol. Genet. 5, 1093–1099.
Dragatsis, I., Efstratiadis, A., and Zeitlin, A. (1998). Mouse mutant embryos lacking huntingtin are rescued from lethality by wild-type extraembryonic tissues. Development 125, 1529–1539.
Metzler, M., Chen, N., Helgason, C. D., Graham, R. K., Nichol, K., McCutcheon, K., et al. (1999) Life without huntingtin, normal differentiation into functional neurons. J. Neurochem. 72, 1009–1018.
Bao, J., Sharp, A. H., Wagster, M. V., Becher, M., Schilling, G., Ross, C. A., et al. (1996) Expansion of polyglutamine repeat in huntingtin leads to abnormal protein interactions involving calmodulin. Proc. Natl. Acad. Sci. USA 93, 5037–5042.
Beckingham, K., Lu, A. Q., and Andruss, B. F. (1998) Calcium-binding proteins and development. Biometals 11, 359–73.
Burke, J. R., Enghild, J. J., Martin, M. E., Jou, Y. S., Myers, R. M., Roses, A. D., et al. (1996) Huntingtin and DRPLA proteins selectively interact with the enzyme GAPDH. Nat. Med. 2, 347–350.
Sirover, M. A. (1996) Emerging new funcitons of the glycolytic protein, glyceraldehyde-3-phosphatate dehydrogenase, in mammalian cells. Life Sci. 58, 2271–2277.
Tukamoto, T., Nukina, N., Ide, K., and Kanazawa, I. (1997) Huntington’s disease gene product, huntingtin, associates with microtubules in vitro. Brain Res. Mol. Brain Res. 51, 8–14.
Liu, Y. F., Deth, R. C., and Devys, D. (1997) SH3 domain—dependent association of huntingtin with epidermal growth factor receptor signaling complexes. J. Biol. Chem. 272, 8121–8124.
Wang, Z. and Moran, M. F. (1996) Requirement for the adapter protein GRB2 in EGF receptor endocytosis. Science 272, 1935–1939.
Li, X. J., Li, S. H., Sharp, A. H., Nucifora, F. C., Jr., Schilling, G., Lanahan, A., et al. (1995) A huntingtin—associated protein enriched in brain with implications for pathology. Nature 378, 398–402.
Bertaux, F., Sharp, A., Ross, C. A., Lehrach, H., Bates, G. P., and Wanker, E. (1998) HAP1-huntingtin interactions do not contribute to the molecular pathology in Huntington’s disease transgenic mice. FEBS Letters 426, 229–232.
Li, S. H., Hossein, S. H., Gutekunst, C. A., Hersch, S. M., Ferrante, R. J., and Li, X. J. (1998) A human HAP1 homologue. J. Biol. Chem. 273, 19220–19227.
Engelender, S., Sharp, A. H., Colomer, V., Tokito, M. K., Lanahan, A., Worley, P., et al. (1997) Huntingtin-associated protein 1 (HAP1) interacts with the p150Glued subunit of dynactin. Hum. Mol. Genet. 6, 2205–2212.
Li, S. H., Gutekunst, C. A., Hersch, S. M., and Li, X. J. (1998) Interaction of huntingtin-associated protein with dynactin P150. J. Neurosci. 18, 1261–1269.
Karki, S. and Holzbaur, E. L. (1995) Affinity chromatography demonstrates a direct binding between cytoplasmic dynein and the dynactin complex. J. Biol. Chem. 270, 28806–28811.
Vaughan, K. T. and Vallee, R. B. (1995) Cytoplasmic dynein binds dynactin through a direct interaction between the intermediate chains and p150Glued. J. Cell Biol. 131, 1507–1516.
Kalchman, M. A., Koide, H. B., McCutcheon, K., Graham, R. K., Nichol, K., Nishiyama, K., et al. (1997) HIP1, a human homologue of S. cerevisiae Sla2p, interacts with membrane—associated huntingtin in the brain. Nat. Genet. 16, 44–53.
Wanker, E. E., Rovira, C., Scherzinger, E., Hasenbank, R., Walter, S., Tait, D., et al. (1997) HIP-I, a huntingtin interacting protein isolated by the yeast two-hybrid system. Hum. Mol. Genet. 6, 487–495.
Holtzman, D. A., Yang, S., and Drubin, D. G. (1993) Synthetic—lethal interactions identify two novel genes, SLA1 and SLA2, that control membrane cytoskeleton assembly in Saccharomyces cerevisiae. J. Cell Biol. 122, 635–644.
Li, R., Zheng, Y., and Drubin, D. G. (1995) Regulation of cortical actin cytoskeleton assembly during polarized cell growth in budding yeast. J. Cell Biol. 128, 599–615.
Na, S., Hincapie, M., McCusker, J. H., and Haber, J. E. (1995) MOP2 (SLA2) affects the abundance of the plasma membrane H(+)—ATPase of Saccharomyces cerevisiae. J. Biol. Chem. 270, 6815–6823.
Wesp, A., Hicke, L., Palecek, J., Lombardi, R., Aust, T., Munn, A. L., et al. (1997) End4p/S1a2p interacts with actin—associated proteins for endocytosis in Saccharomyces cerevisiae. Mol. Biol. Cell. 8, 2291–2306.
Kalchman, M. A., Graham, R. K., Xia, G., Koide, H. B., Hodgson, J. G., Graham, K. C., et al. (1996) Huntingtin is ubiquitinated and interacts with a specific ubiquitin-conjugating enzyme. J. Biol. Chem. 271, 19385–19394.
Hochstrasser, M. (1996) Ubiquitin-dependent protein degradation. Annu. Rev. Genet. 30, 405–439.
Hicke, L. and Riezman, H. (1996) Ubiquitination of a yeast plasma membrane receptor signals its ligand-stimulated endocytosis. Cell 84, 277–287.
Sittler, A., Walter, S., Wedemeyer, N., Hasenbank, R., Scherzinger, E., Eickhoff, H., et al. (1998) SH3GL3 associates with the huntingtin exon 1 protein and promotes the formation of polygln-containing protein aggegates. Mol. Cell 2, 427–436.
Ringstad, N., Nemoto, Y., and De Camilli, P. (1997). the SH3p4/Sh3p8/SH3p13 protein family, binding partners for synaptojanin and dynamin via a Grb2—like Src homology 3 domain. Proc. Natl. Acad. Sci. USA 94, 8569–8574.
Zechner, U., Scheel, S., Hemberger, M., Hopp, M., Haaf, T., Fundele, R, et al. (1998) Characterization of the mouse Src homology 3 domain gene Sh3d2c on Chr 7 demonstrates coexpression with huntingtin in the brain and identifies the processed pseudogene Sh3d2c-psl on Chr 2. Genomics 54, 505–510.
Faber, P. W., Barnes, G. T., Srinidhi, J., Gusella, J. F., and MacDonald, M. E. (1998) Huntingtin interacts with a family of WW domain proteins. Hum. Mol. Genet. 7, 1463–1474.
Bedford, M. T., Chan, D. C., and Leder, P. (1997) FBP WW domains and the Abl SH3 domain bind to a specific class of proline—rich ligands. EMBO J. 16, 2376–2383.
Bedford, M. T., Reed, R., and Leder, P. (1998) WW domain-mediated interactions reveal a spliceosome-assocated protein that binds a third class of proline-rich motif, The proline glycine and methionine-rich motif. Proc. Natl. Acad. Sci. USA 95, 10602–10607.
Kao, H. Y. and Siliciano, P. G. (1996) Identification of Prp40, a novel essential yeast splicing factor associated with the U1 small nuclear ribonucleoprotein particle. Mol. Cell. Biol. 16, 960–967.
Passani, L. A., Bedford, M. T., Faber, P. W., McGinnis, K. M., Gusella, J. F., Vonsattel, J.-P., and MacDonald, M. E. (2000) Huntingtin’s WW domain partners in HD post-mortem brain fulfill genetic criteria for direct involvement in HD pathogenesis. Hum. Mol. Genet.,in press.
Chan, D. C., Bedford, M. T., and Leder P. (1996) Formin binding proteins bear WWP/WW domains that bind proline-rich peptides and functionally resemble SH3 domains. EMBO J. 15, 1045–1054.
Gaugler, B., Van den Eynde, B., van der Bruggen, P., Romero, P., Gaforio, J. J., De Plaen, E., et al. (1994) Human MAGE-3 codes for an antigen recognized on a melanoma by autologous cytolytic T lymphocytes J. Exp. Med. 179, 921–930.
Tahara, K., Mori, M., Sadanaga, N., Sakamoto, Y., Kitano, S., and Makuuchi, M. (1999) Expression of MAGE gene family in human hepatocellular carcinoma. Cancer 15, 1234–1240.
Kominami, K., DeMartino, G. N., Moomaw, C. R., Slaughter, C. A., Shimbara, N., Fujimuro, M., et al. (1995) Ninlp, a regulatory subunit of the 26S proteasome, is necessary for activation of Cdc28p kinase of Saccharomyces cerevisiae. EMBO J. 14, 3105–3115.
Robinson, M. S. (1989) Cloning of cDNAs encoding two related 100-kD coated vesicle proteins (alpha-adaptins). J Cell Biol. 108, 833–842.
Ball, C. L., Hunt, S. P., and Robinson, M. S. (1995) Expression and localization of alpha-adaptin isoforms. J. Cell Sci. 108, 2865–2875.
Dornan, S., Jackson, A. P., and Gay, N. J. (1997) Alpha-adaptin, a marker for endocytosis, is expressed in complex patterns during Drosophila development. Mol. Biol.Cell 8, 1391–1403.
Keon, B. H., Schafer, S., Kuhn, C., Grund, C., and Franke, W. W. (1996) Symplekin, a novel type of tight junction plaque protein. J. Cell Biol. 134, 1003–1018.
Yongan, L., Kang, J., and Horwitz, M. S. (1998) Interaction of an adenovirus E3 14.7 kilodalton protein with a novel tumor necrosis factor alpha-inducible cellular protein containing leucine zipper domains. Mol. Cell. Biol. 18, 1601–1610.
Wold, W. S. M., Hermiston, T. W., and Tollefson, A. E. (1994) Adenovirus proteins that subvert host defenses. Trends Microbiol. 2, 437–443.
Boutell, J. M., Wood, J. D., Harper, P. S., and Jones, A. L. (1998) Huntingtin interacts with cystathionine beta-synthase. Hum. Mol. Genet. 7, 371–378.
Bao, L., Vlcek, C., Paces, V., and Kraus, J. P. (1998) Identification and tissue distribution of human cystathionine beta-synthase mRNA isoforms. Arch Biochem. Biophys. 350, 95–103.
Fields, S. and Sternglanz, R. (1994) The two-hybrid system, an assay for protein-protein interactions. Trends Genet. 10, 286–292.
Pawson, T. (1995) Protein modules and signaling networks. Nature 373, 573–578.
Ren, R., Mayer, B. J., Cicchetti, P., and Baltimore, D. (1993) Identification of a ten-amino acid proline rich SH3 binding site. Science 259, 1157–1161.
Colomer, V., Engelender, S., Sharp, A. H., Duan, K., Cooper, J. K., Lanahan, A., et al. (1997) Huntingtin-associated protein 1 (HAP1) binds to a Trio-like polypeptide, with a rac 1 guanine nucleotide exchange factor domain. Hum. Mol. Genet. 6, 1519–1525.
Ross, T. S., Bernard, O. A., Berger, R., and Gilliland, D. G. (1998) Fusion of huntingtin interacting protein 1 to platelet-derived growth factor beta receptro (PDGFbetaR) in chronic myelomonocytic leukemia with t(5;7)(g33;g11. 2). Blood 91, 4419–4426.
Bedford, M. and Leder, P. (1998) The FF domain, a novel motif that often accompanies WW domains. Trends Biochem. Sci. 24, 264, 265.
Barth, A. I., Nathke, I. S., and Nelson, J. (1997) Cadherins, catenins and APC protein, interplay between cytoskeletal complexes and signalling pathways. Curr. Opin. Cell Biol. 9, 683–690.
Persichetti, F., Trettel, F., Huang, C. C., Fraefel, C., Timmers, H. T. M., Gusella, J. F., et al. (1999) Mutant huntingtin forms in vivo complexes with distinct context—dependent conformations of the polyglutamine segment. Neurobiol. Dis. 6, 364–375.
Trottier, Y., Lutz, Y., Stevanin, G., Imbert, G., Devys, D., Cancel, G., et al. (1995). Polyglutamine expansion as a pathological epitope in Huntington’s disease and four dominant cerebellar ataxias. Nature 378, 403–406.
Huang, C. C., Faber, P. W., Persichetti, F., Mittal, V., Vonsattel, J-P., MacDonald, M. E., et al. (1998) Amyloid formation by mutant huntingtin, threshold, progressivity and recruitment of normal polyglutamine proteins. Somat. Cell Mol. Genet. in press.
Scherzinger, E., Lurz, R., Turmaine, M., Mangiarini, L., Hollenbach, B., Hasenbank, R., et al. (1997) Huntingtin—encoded polyglutamine expansions form amyloid—like protein aggregates in vitro and in vivo. Cell 90, 549–558.
DiFiglia, M., Sapp, E., Chase, K. O., Davies, S. W., Bates, G. P., Vonsattel, J. P., et al. (1997). Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277, 1990–1993.
Sapp, E., Penney, B. A. J., Young, A., Aronin, N., Vonsattel, J-P., and DiFiglia, M. (1999) Axonal transport of N-terminal huntingtin suggests early pathology of corticostriatal projections in Huntington’s disease. J. Neuropathol. Exp. Neurol. 58, 165–173.
Sieradzan, K. A., Mechan, A. O., Jones, L., Wanker, E. E., Nukina, N., and Mann, D. M. (1999) Huntington’s disease intranuclear inclusions contain truncated ubiquintated huntingtin protein. Exp. Neurol. 156, 92–99.
Maat-Schieman, M. L., Dorsman, J. C., Smoor, M. A., Siesling, S., Van Duinen, S. G., Verschuuren, J. J., et al. (1999) Distribution of inclusions in neuronal nuclei and dystrophic neurites in Huntington’s disease brain. J. Neuropathol. Exp. Neurol. 58, 129–137.
Gutekunst, C.-A., Li, S-H., Yi, H., Mulroy, J. S., Kuemmerle, S., Jones, R., et al. (1999) Nuclear and neuropil aggregates in Huntington’s disease, relationship to neuropathology. J. Neurosci. 19, 2522–2534.
Goldberg, Y. P., Nicholson, D. W., Rasper, D. M., Kalchman, M. A., Koide, H. B., Graham, R. K., et al. (1996) Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. Nat. Genet. 13, 442–449.
Lunkes, A. and Mandel, J. L. (1998) A cellular model that recapitulates major pathogenic steps of Huntington’s disease. Hum. Mol. Genet. 7, 1355–1361.
Reddy, P. H., Williams, M., Charles, V., Garrett, L., Pike-Buchanan, L., Whetsell, W. O. Jr., et al. (1998) Behavioral abnormalities and selective neuronal loss in HD transgenic mice expressing full-length HD cDNA. Nature Genet. 20, 198–202.
Hodgson, J. G., Agopyan, N., Gutekunst, C-A., Leavitt, B. R., LePiane, F., Singaraja, R., et al. (1999) A YAC mouse model for Huntington’s disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron 23, 181–192.
Shelbourne, P. F., Killeen, N., Hevner, R. F., Johnston, H. M., Tecott, L., Lewandoski, M., et al. (1999) A Huntington’s disease CAG expansion at the murine Hdh locus is unstable and associated with behavioural abnormalities in mice. Hum. Mol. Genet. 8, 763–774.
Levine, M. S., Klaptein, G. J., Koppel, A., Gruen, E., Cepeda, C., Vargas, M. E., et al. (1999) Enhanced sensitivity to N-methyl-D-asparate receptor activation in transgenic and knockin mice models to Huntington’s disease. J. Neurosci. Res. 58, 515–532.
Wheeler, V. C., White, J. K., Gutekunst, C. A., Vrbanac, V., Weaver, M., Li, X. J., Li, S. H., Yi, H., Vonsattel, J. P., Gusella, J. F., Hersch, S., Auerbach, W., Joyner, A. L., and MacDonald, M. E. (2000) Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in mice. Hum. Mol. Genet. 9, 503–513.
Feng, Y. and Davis, N. G. (2000) Akrlp and the Type I casein kinases act prior to the ubiquitination step of yeast endocytosis: Akrlp is required for kinase localization to the plasma membrane. Mol. Cell Biol. 20, 5350–5359.
Takagaki, Y. and Manley, J. L. (2000) Complex protein interactions within the human polyadenylation machinery identify a novel component. Mol. Cell Biol. 20, 1515–1525.
Boutell, J. M., Thomas, P., Neal, J. W., Weston, V. J., Duce, J., Harper, P. S., and Jones, A. L. (1999) Aberrant interactions of transcriptional repressor proteins with the Huntington’s disease gene product, huntingtin. Hum. Mol. Genet. 8, 1647–1655.
Rights and permissions
Copyright information
© 2001 Springer Science+Business Media New York
About this chapter
Cite this chapter
MacDonald, M.E., Passani, L., Hilditch-Maguire, P. (2001). Huntingtin-Associated Proteins. In: Molecular Mechanisms of Neurodegenerative Diseases. Contemporary Clinical Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-006-3_15
Download citation
DOI: https://doi.org/10.1007/978-1-59259-006-3_15
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61737-197-4
Online ISBN: 978-1-59259-006-3
eBook Packages: Springer Book Archive