Preferences help
enabled [disable] Abstract
Number of results
2013 | 60 | 1 | 51-55
Article title

Changes in kinesin expression in the CNS of mice with dynein heavy chain 1 mutation

Title variants
Languages of publication
Dysfunction of fast axonal transport, vital for motor neurons, may lead to neurodegeneration. Anterograde transport is mediated by N-kinesins (KIFs), while retrograde transport by dynein 1 and, to a minor extent, by C-kinesins. In our earlier studies we observed changes in expression of N- and C-kinesins (KIF5A, 5C, C2) in G93ASOD1-linked mouse model of motor neuron degeneration. In the present work we analyze the profile of expression of the same kinesins in mice with a dynein 1 heavy chain mutation (Dync1h1, called Cra1), presenting similar clinical symptoms, and in Cra1/SOD1 mice with milder disease progression than SOD1 transgenics. We found significantly higher levels of mRNA for KIF5A and KIF5C but not the KIFC2 in the frontal cortex of symptomatic Cra1/+ mice (aged 365 days) compared to the wild-type controls. No changes in kinesin expression were found in the spinal cord of any age group and only mild changes in the hippocampus. The expression of kinesins in the cerebellum of the presymptomatic and symptomatic mice (aged 140 and 365 days, respectively) was much lower than in age-matched controls. In Cra1/SOD1 mice the changes in KIFs expression were similar or more severe than in the Cra1/+ groups, and they also appeared in the spinal cord. Thus, in mice with the Dync1h1 mutation, which impairs dynein 1-dependent retrograde transport, expression of kinesin mRNA is affected in various structures of the CNS and the changes are similar or milder than in mice with double Dync1h1/hSOD1G93A mutations.
Physical description
  • Chair and Department of Neurology and Neurodegenerative Diseases Research Group, Medical University of Warsaw, Warsaw, Poland
  • Chair and Department of Biochemistry and Neurodegenerative Diseases Research Group, Medical University of Warsaw, Warsaw, Poland
  • Chair and Department of Biochemistry, Medical University of Warsaw, Warsaw, Poland
  • Chair and Department of Biochemistry and Neurodegenerative Diseases Research Group, Medical University of Warsaw, Warsaw, Poland
  • Andersen P (2006) Amyotrophic lateral sclerosis associated with mutations in the CuZn superoxide dismutase gene. Current Neurol Neurosci Rep 6: 37-46.
  • Barańczyk-Kuźma A, Usarek E, Kuźma-Kozakiewcz M, Kaźmierczak B, Gajewska B, Schwalenstocker B, Ludolph AC (2007) Age-related changes in tau expression in transgenic mouse model of amyotrophic lateral sclerosis. Neurochem Res 32: 415-421.
  • Coleman M (2005) Axon degeneration mechanisms: commonality amid diversity. Nat Rev Neurosci 6: 889-898.
  • Courchesne SL, Pazyra-Murphy MF, Lee DJ, Segal RA (2011) Neuromuscular junction defects in mice with mutation of dynein heavy chain 1. PLoS One. 4; 6: e16753.
  • Dal Canto MC, Gurney ME (1995) Neuropathological changes in two lines of mice carrying a transgene for mutant human CuZn SOD and in mice overexpressing wild type human SOD: a model of familial amyotrophic lateral sclerosis. Brain Res 676: 25-40.
  • Dupuis L, Fergani A, Braunstein KE, Eschbach J, Holl N, Rene N, Gonzalez De Aguilar JL, Zoerner B, Schwalenstocker B, Ludolph AC, Loeffler JP (2009) Mice with a mutation in the dynein heavy chain 1 gene display sensory neuropathy but lack motor neuron disease. Exp Neurol 215: 146-152.
  • El-Kadi AM, Soura V, Hafezparast M (2007) Defective axonal transport in motor neurodiseas. J Neurosc Res 85: 2557-2566.
  • Eschbach J, Dupuis L (2011) Cytoplasmic dynein in neurodegeneration. Pharmacol Ther 130: 348-363.
  • Gurney ME, Pu H, Chiu AY, Dal Canto MC, Polchow CY, Alexander DD (1994) Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science 264: 1772-1775.
  • Hafezparast M, Klocke R, Ruhrberg C, Marquardt A, Ahmad-Annuar A , Bowen S, Lalli G, Witherden AS, Hummerich H, Nicholson S, Morgan PJ, Oozageer R, Priestley JV, Averill S, King RV, Ball S, Peters J, Toda T, Yamamoto A, Hiraoka Y, Augustin M, Korthaus D, Wattler S, Wabnitz P, Dickneite C, Lampel S, Boehme G, Peraus G, Popp A, Rudelius M, Schlegel J, Fuchs H, Hrabe de Angelis M, Schiavo DT, Shima G, Russ AP, Stumm G, Martin JE, Fisher EM (2003) Mutations in dynein link motor neuron degeneration to defects in retrograde transport. Science 300: 808-881.
  • Hanlon DW, Yang Z, Goldstein LS (1997) Characterization of KIFC2, a neuronal kinesin superfamily member in mouse. Neuron 18: 439-451.
  • Hirokawa N, Shiomura Y, Okabe S (1988) Tau proteins: the molecular structure and mode of binding on microtubules. J Cell Biol 107: 1449-1459.
  • Hirokawa N, Tekamura R (2004) Molecular motors in neuronal development, intracellular transport and diseases. Cur Op Neurol 14: 564-573.
  • Hirokawa N, Noda Y, Tanaka Y, Niwa S (2009) Kinesin superfamily motor proteins and intracellular transport. Nat Rev Mol Cell Biol 10: 682-696.
  • Hrabe de Angelis MH, Flaswinkel H, Fuchs H, Rathkolb B, SoewartoD, Marschall S, Heffner S, Pargent W, Wuensch, K Jung M, Reis A, Richter T, Alessandrini F, Jakob T, Fuchs E, Kolb H, Kremmer E, Schaeble K, Rollinski B, Roscher A, Peters C, Meitinger T, Strom T, Steckler T, Holsboer F, Klopstock T, Gekeler F, Schindewolf C, Jung TM, Avraham K, Behrendt H, Ring J, Zimmer A, Schughart K, Pfeffer K, Wolf E, Balling R (2000) Genome-wide, large-scale production of mutant mice by ENU mutagenesis. Nat Genet 25: 444-447.
  • Hua W, Young EC, Fleming ML, Gelles J (1997) Coupling of kinesin steps to ATP hydrolysis. Nature 388: 390-393.
  • Ikenaka K, Katsuno M, Kawai K, Ishigaki S, Tanaka F, Sobue G (2012) Disruption of axonal transport in motor neuron diseases. Int J Mol Sci 13: 1225-1238.
  • Ince PG, Highley JR, Kirby J, Wharton SB, Takahashi H, Strong MJ, Shaw PJ (2011) Molecular pathology and genetic advances in amyotrophic lateral sclerosis: an emerging molecular pathway and the significance of glial pathology. Acta Neuropathol 122: 657-671.
  • LaMonte BH, Wallace KE, Holloway BA, Shelly SS, Ascaño J, Tokito M, Van Winkle T, Howland DS, Holzbaur EL (2002) Disruption of dynein/dynactin inhibits axonal transport in motor neurons causing late-onset progressive degeneration. Neuron 34: 715-727.
  • Kanai Y, Okada Y, Tanaka Y, Harada A, Terada S, Hirokawa N (2000) KIF5C, a novel neuronal kinesin enriched in motor neurons. J Neurosci 20: 6374-6384.
  • Kieran D, Hafezparast M, Bohnert S, Dick JR, Martin J, Schiavo G, Fisher EM, Greensmith L (2005) A mutation in dynein rescues axonal transport defect and extends the life span of ALS mice. J Cell Biol 169: 561-567.
  • Kaźmierczak B, Kuźma-Kozakiewicz M, Usarek E, Barańczyk-Kuźma A (2011) Differences in glutathione S-transferase pi expression in transgenic mice with symptoms of neurodegeneration. Acta Biochim Pol 58: 621-626.
  • Kuźma-Kozakiewicz M, Usarek E, Ludolph AC, Barańczyk-Kuźma A (2011) Mice with mutation in dynein heavy chain 1 do not share the same tau expression pattern with mice with SOD1-related motor neuron disease. Neurochem Res 36: 978-985.
  • Kuźma-Kozakiewicz M, Chudy A, Gajewska B, Dziewulska D, Usarek E, Barańczyk-Kuźma A (2012) Kinesins expression in the central nervous system of humans and transgenic hSOD1G93A mice with amyotrophic lateral sclerosis. Neurodegener Dis online 21 Sept. 2012, DOI: 10.1159/000339529.
  • Magnani E, Fan J, Gasparini L, Golding M et al. (2007) Interaction of tau protein with the dynactin complex. EMBO J 26: 4546-4554.
  • Mulder DW, Kurland LT, Offord KP, Beard CM (1986) Familial adult motor neuron disease: amyotrophic lateral sclerosis. Neurology 36: 511-517.
  • Nicotera P, Lipton SA (1999) Excitotoxins in neuronal apoptosis and necrosis, J Cereb Blood Flow Metab 19: 583-591.
  • Perlson E, Maday S, Fu MM, Moughamian AJ, Holzbaur EL (2010) Retrograde axonal transport: pathways to cell death? Trends Neurosci 33: 335-344.
  • Puls I., Jonnakuty C., LaMonte BH, Holzbaur EL, Tokito M, Mann E, Floete MK, Bidus K, Drayna D, Oh SJ, Brown RH, Ludlow CL, Fischbeck KH (2003) Mutant dynactin in motor neuron disease. Nat Genet 33: 455-456.
  • Saito N, Okada Y, Noda Y, Kinoshita Y, Kondo S, Hirokawa N (1997) KIFC2 is a novel neuron-specific C-terminal type kinesin superfamily motor for dendritic transport of multivesicular body-like organelles. Neuron 18: 425-438.
  • Teuchert M, Fischer D, Schwalenstoecker B, Habisch HJ, Bockers TM, Ludolph AC (2006) A dynein mutation attenuates motor neuron degeneration in SOD1G93A mice. Exp Neurol 198: 271-274.
  • Tu PH, Raju P, Robinson KA, Gurney ME, Trojanowski JQ, Lee VM (1996) Transgenic mice carrying a human mutant superoxide dismutase transgene develop neuronal cytoskeletal pathology resembling human amyotrophic lateral sclerosis lesions. Proc Nat Acad Sci USA 93: 3155-3160.
  • Vaughan KT (2005) Microtubule plus ends, motors, and traffic of Golgi membranes. Biochim Biophys Acta 1744: 316-324.
  • Vale RD, Fletterick RJ (1997) The design plan of kinesin motors. Annu Rev Cell Dev Biol 13: 745-777.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.