Mice deficient in the Rab5 guanine nucleotide exchange factor ALS2/alsin exhibit age-dependent neurological deficits and altered endosome trafficking

Human Molecular Genetics

Volumn 15, Issue 2, 2006, Pages 233-250

  Hadano, Shinji ^a,b   Benn, Susanna C ^c   Kakuta, Shigeru ^d   Otomo, Asako ^a   Sudo, Katsuko ^d,h   Kunita, Ryota ^a,b   Suzuki Utsunomiya, Kyoko ^a   Mizumura, Hikaru ^b   Shefner, Jeremy M ^e   Cox, Gregory A ^f   Iwakura, Yoichiro ^d   Brown Jr , Robert H ^c   Ikeda, Joh E ^a,b,g  

^a TOKAI UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^b JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

^c MASSACHUSETTS GENERAL HOSPITAL   (United States)

^d UNIVERSITY OF TOKYO   (Japan)

^e State University of New York Upstate Medical University: College of Medicine   (United States)

^f JACKSON LABORATORY   (United States)

^g UNIVERSITY OF OTTAWA   (Canada)

^h TOKYO MEDICAL UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ALSIN; EPIDERMAL GROWTH FACTOR; GENE PRODUCT; GUANINE NUCLEOTIDE EXCHANGE FACTOR; GUANOSINE TRIPHOSPHATASE; RAB PROTEIN; REGULATOR PROTEIN; UNCLASSIFIED DRUG;

AGING; ALS2 GENE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASTROCYTOSIS; CELL ACTIVATION; CELL LOSS; CELL VACUOLE; CELL VIABILITY; CONTROLLED STUDY; ELECTROPHYSIOLOGY; ENDOCYTOSIS; ENDOSOME; FEMALE; IMMUNOHISTOCHEMISTRY; INTRACELLULAR TRANSPORT; MALE; MAMMALIAN GENETICS; MICROGLIA; MOTOR DYSFUNCTION; MOUSE; NEUROLOGIC DISEASE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN DEFECT; PROTEIN FAMILY; PURKINJE CELL; SPINAL CORD MOTONEURON;

AGE FACTORS; ANALYSIS OF VARIANCE; ANIMALS; BIOLOGICAL TRANSPORT; BLOTTING, SOUTHERN; BLOTTING, WESTERN; CARRIER PROTEINS; DNA PRIMERS; ELECTROPHYSIOLOGY; ENDOSOMES; EPIDERMAL GROWTH FACTOR; IMMUNOHISTOCHEMISTRY; MICE; MICE, KNOCKOUT; MOTOR NEURONS; NERVOUS SYSTEM DISEASES; PURKINJE CELLS;

ANIMALIA; MAMMALIA;

EID: 31144448704     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddi440     Document Type: Article

References (56)

1. Hadano, S., Hand, C.K., Osuga, H., Yanagisawa, Y., Otomo, A., Devon, R.S., Miyamoto, N., Showguchi-Miyata, J., Okada, Y., Singaraja, R. et al. (2001) A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2. Nat. Genet., 29, 166-173.
2. Yang, Y., Hentati, A., Deng, H.X., Dabbagh, O., Sasaki, T., Hirano, M., Hung, W.Y., Ouahchi, K., Yan, J., Azim, A.C. et al. (2001) The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. Nat. Genet., 29, 160-165.
3. Ben-Hamida, M., Hentati, F. and Ben-Hamida, C. (1990) Hereditary motor system diseases (chronic juvenile amyotrophic lateral sclerosis). Brain, 113, 347-363.
4. Lerman-Sagie, T., Filiano, J., Smith, D.W. and Korson, M. (1996) Infantile onset of hereditary ascending spastic paralysis with bulbar involvement. J. Child Neurol., 11, 54-57.
5. Eymard-Pierre, E., Lesca, G., Dollet, S., Santorelli, F.M., di Capua, M., Bertini, E. and Boespflug-Tanguy, O. (2002) Infantile-onset ascending hereditary spastic paralysis is associated with mutations in the alsin gene. Am. J. Hum. Genet., 71, 518-527.
6. Lesca, G., Eymard-Pierre, E., Santorelli, F.M., Cusmai, R., Di Capua, M., Valente, E.M., Attia-Sobol, J., Plauchu, H. Leuzzi, V. Ponzone, A. et al. (2003) Infantile ascending hereditary spastic paralysis (IAHSP): clinical features in 11 families. Neurology, 60, 674-682.
7. Devon, R.S., Helm, J.R., Rouleau, G.A., Leitner, Y., Lerman-Sagie, T., Lev, D. and Hayden, M.R. (2003) The first nonsense mutation in alsin results in a homogeneous phenotype of infantile-onset ascending spastic paralysis with bulbar involvement in two siblings. Clin. Genet., 64, 210-215.
8. Gros-Louis, F., Meijer, I.A., Hand, C.K., Dube, M.P., MacGregor, D.L., Seni, M.H., Devon, R.S., Hayden, M.R., Andermann, F., Andermann, E. et al. (2003) An ALS2 gene mutation causes hereditary spastic paraplegia in a Pakistani kindred. Ann. Neurol., 53, 144-145.
9. Kress, J.A., Kühnlein, P., Winter, P., Ludolph, A.C., Kassubek, J., Müller, U. and Sperfeld, A.D. (2005) Novel mutation in the ALS2 gene in juvenile amyotrophic lateral sclerosis. Ann. Neurol., 58, 800-803.
10. Cleveland, D.W. and Rothstein, J.D. (2001) From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nat. Rev. Neurosci., 2, 806-819.
11. Verma, A. and Bradley, W.G. (2001) Atypical motor neuron disease and related motor syndromes. Semin. Neurol., 21, 177-187.
12. Fink, J.K. (2001) Progressive spastic paraparesis: Hereditary spastic paraplegia and its relation to primary and amyotrophic lateral sclerosis. Semin. Neurol., 21, 199-207.
13. Kunst, C.B. (2004) Complex genetics of amyotrophic lateral sclerosis. Am. J. Hum. Genet., 75, 933-947.
14. Ohtsubo, M., Kai, R., Furuno, N., Sekiguchi, T., Sekiguchi, M., Hayashida, H., Kuma, K., Miyata, T., Fukushige, S., Murotsu, T. et al. (1987) Isolation and characterization of the active cDNA of the human cell cycle gene (RCCl) involved in the regulation of onset of chromosome condensation. Genes Dev., 1, 585-593.
15. Schmidt, A. and Hall, A. (2002) Guanine nucleotide exchange factors for Rho GTPases: Turning on the switch. Genes Dev., 16, 1587-1609.
16. Burd, C.G., Mustol, P.A., Schu, P.V. and Emr, S.D. (1996) A yeast protein related to a mammalian Ras-binding protein, Vps9p, is required for localization of vacuolar proteins. Mol. Cell. Biol., 16, 2369-2377.
17. Horiuchi, H., Lippe, R., McBride, H.M., Rubino, M., Woodman, P., Stenmark, H., Rybin, V., Wilm, M., Ashman, K., Mann, M. et al. (1997) A novel Rab5 GDP/GTP exchange factor complexed to Rabaptin-5 links nucleotide exchange to effector recruitment and function. Cell, 90, 1149-1159.
18. Tall, G.G., Barbieri, M.A., Stahl, P.D. and Horazdovsky, B.F. (2001) Ras-activated endocytosis is mediated by the Rab5 guanine nucleotide exchange activity of RIN1. Dev. Cell, 1, 73-82.
19. Saito, K., Murai, J., Kajiho, H., Kontani, K., Kurosu, H. and Katada, T. (2002) A novel binding protein composed of homophilic tetramer exhibits unique properties for the small GTPase Rab5. J. Biol. Chem., 277, 3412-3418.
20. Kajiho, H., Saito, K., Tsujita, K., Kontani, K., Araki, Y., Kurosu, H. and Katada, T. (2003) RIN3: A novel Rab5 GEF interacting with amphiphysin II involved in the early endocytic pathway. J. Cell Sci., 116, 4159-4168.
21. Sato, M., Sato, K., Fonarev, P., Huang, C.-J., Liou, W. and Grant, B.D. (2005) Caenorhabditis elegans RME-6 is a novel regulator of RAB-5 at the clathrin-coated pit. Nat. Cell Biol., 7, 559-569.
22. Otomo, A., Hadano, S., Okada, T., Mizumura, H., Kunita, R., Nishijima, H., Showguchi-Miyata, J., Yanagisawa, Y., Kohiki, E., Suga, E. et al. (2003) ALS2, a novel guanine nucleotide exchange factor for the small GTPase Rab5, is implicated in endosomal dynamics. Hum. Mol. Genet., 12, 1671-1687.
23. Kunita, R., Otomo, A., Mizumura, H., Suzuki, K., Showguchi-Miyata, J., Yanagisawa, Y., Hadano, S. and Ikeda, J.-E. (2004) Homo-oligomerization of ALS2 through its unique carboxy-terminal region is essential for the ALS2-associated Rab5 guanine nucleotide exchange activity and its regulatory function on endosome trafficking. J. Biol. Chem., 279, 38626-38635.
24. Yamanaka, K., Vande Velde, C., Eymard-Pierre, E., Bertini, E., Boespflug-Tanguy, O. and Cleveland, D.W. (2003) Unstable mutants in the peripheral endosomal membrane component ALS2 cause early-onset motor neuron disease. Proc. Natl. Acad. Sci. USA, 100, 16041-16046.
25. Topp, J.D., Gray, N.W., Gerard, R.D. and Horazdovsky, B.F. (2004) Alsin is a Rab5 and Rac1 guanine nucleotide exchange factor. J. Biol. Chem., 279, 24612-24623.
26. Millecamps, S., Gentil, B.J., Gros-Louis, F., Rouleau, G. and Julien, J.P. (2005) Alsin is partially associated with centrosome in human cells. Biochim. Biophys. Acta., 1745, 84-100.
27. Kanekura, K., Hashimoto, Y., Kita, Y., Sasabe, J., Aiso, S., Nishimoto, I. and Matsuoka, M. (2005) A Rac1/phosphatidylinositol 3-kinase/Akt3 anti-apoptotic pathway, triggered by alsinLF, the product of the ALS2 gene, antagonizes Cu/Zn-superoxide dismutase (SOD1) mutant-induced motoneuronal cell death. J. Biol. Chem., 280, 4532-4543.
28. Tudor, E.L., Perkinton, M.S., Schmidt, A., Ackerley, S., Brownlees, J., Jacobsen, N.J.O., Byers, H.L., Ward, M., Hall, A., Leigh, P. N. et al. (2005) ALS2/Alsin regulates Rac-PAK signaling and neurite outgrowth. J. Biol. Chem., 280, 34735-34740.
29. Kanekura, K., Hashimoto, Y., Niikura, T., Aiso, S., Matsuoka, M. and Nishimoto, I. (2004) Alsin, the product of ALS2 gene, suppresses SOD1 mutant neurotoxicity through RhoGEF domain by interacting with SOD1 mutants. J. Biol. Chem., 279, 19247-19256.
30. Leavitt, B.R. (2002) Hereditary motor neuron disease caused by mutations in the ALS2 gene: 'the long and the short of it". Clin. Genet., 62, 265-269.
31. Devon, R.S., Schwab, C., Topp, J.D., Orban, P.C., Yang, Y.-Z., Pape, T.D., Helm, J.R., Davidson, T.-L., Rogers, D.A., Gros-Louis, F. et al. (2005) Cross-species characterization of the ALS2 gene and analysis of its pattern of expression in development and adulthood. Neurobiol. Dis., 18, 243-257.
32. Strausberg, R.L., Feingold, E.A., Grouse, L.H., Derge, J.G., Klausner, R.D., Collins, F.S., Wagner, L., Shenmen, C.M., Schuler, G. D., Altschul, S. F. et al. (2002) Generation and initial analysis of more than 15 000 full-length human and mouse cDNA sequences. Proc. Natl Acad. Sci. USA, 99, 16899-16903.
33. Hadano, S., Otomo, A., Suzuki-Utsunomiya, K., Kunita, R., Yanagisawa, Y., Showguchi-Miyata, J., Mizumura, H. and Ikeda, J.-E. (2004) ALS2CL, the novel protein highly homologous to the carboxy-terminal half of ALS2, binds to Rab5 and modulates endosome dynamics. FEBS Lett., 575, 64-70.
34. Zerial, M. and McBride, H. (2001) Rab proteins as membrane organizers. Nat. Rev. Mol. Cell Biol., 2, 107-117.
35. Nishimura, T., Fukata, Y., Kato, K., Yamaguchi, T., Matsuura, Y., Kamiguchi, H. and Kaibuchi, K. (2003) CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth. Nat. Cell Biol., 5, 819-826.
36. Cai, H., Lin, X., Xie, C., Laird, F.M., Lai, C., Wen, H., Chiang, H.-C., Shim, H., Farah, M.H., Hoke, A. et al. (2005) Loss of ALS2 function is insufficient to trigger motor neuron degeneration in knock-out mice but predisposes neurons to oxidative stress. J. Neurosci., 25, 7567-7574.
37. Lipp, H.-P. and Wolfer, D.P. (2003) Genetic background problems in the analysis of congnitive and neuronal changes in genetically modified mice. Clin. Neurosci. Res., 3, 223-231.
38. Shefner, J.M. (2001) Motor unit number estimation in human neurological diseases and animal models. Clin. Neurophysiol., 112, 955-964.
39. Fischer, L.R., Culver, D.G., Tennant, P., Davis, A.A., Wang, M., Castellano-Sanchez, A., Khan, J., Polak, M.A. and Glass, J.D. (2004) Amyotrophic lateral sclerosis is a distal axonopathy: Evidence in mice and man. Exp. Neurol., 185, 232-240.
40. G1H transgenic mouse model of ALS. J. Neurosci. Res., 79, 694-699.
41. Shefner, J.M., Reaume, A.G., Flood, D.G., Scott, R.W., Kowall, N.W., Ferrante, R.J., Siwek, D.F., Upton-Rice, M. and Brown, R.H., Jr (1999) Mice lacking cytosolic copper/zinc superoxide dismutase display a distinctive motor axonopathy. Neurology, 53, 1239-1246.
42. Yang, H.W. and Lemon, R.N. (2003) An electron microscopic examination of the corticospinal projection to the cervical spinal cord in the rat: lack of evidence for cortico-motoneuronal synapses. Exp. Brain Res., 149, 458-469.
43. Deluca, G.C., Ebers, G.C. and Esiri, M.M. (2004) The extent of axonal loss in the long tracts in hereditary spastic paraplegia. Neuropathol. Appl. Neurobiol., 30, 576-584.
44. Puls, I., Jonnakuty, C., LaMonte, B.H., Holzbaur, E.L., Tokito, M., Mann, E., Floeter, M.K., Bidus, K., Drayna, D., Oh, S.J. et al. (2003) Mutant dynactin in motor neuron disease. Nat. Genet., 33, 455-456.
45. Münch, C., Sedlmeier, R., Meyer, T., Homberg, V., Sperfield, A.D., Kurt, A., Prudlo, J., Peraus, G., Hanemann, C.O., Stumm, G. et al. (2004) Point mutations of the p150 subunit of dynactin (DCTN1) gene in ALS. Neurology., 63, 724-726.
46. Zhao, C., Takita, J., Tanaka, Y., Setou, M., Nakagawa, T., Takeda, S., Yang, H.W., Terada, S., Nakata, T., Takei, Y. et al. (2001) Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bb. Cell, 105, 587-597.
47. LaMonte, B.H., Wallace, K.E., Holloway, B.A., Shelly, S.S., Ascano, J., Tokito, M., Van Winkle, T., Howland, D.S. and Holzbaur, E.L. (2002) Disruption of dynein/dynactin inhibits axonal transport in motor neurons causing late-onset progressive degeneration. Neuron, 34, 715-727.
48. Hafezparast, M., Klocke, R., Ruhrberg, C., Marquardt, A., Ahmad-Annuar, A., Bowen, S., Lalli, G., Witherden, A.S., Hummerich, H., Nicholson, S. et al. (2003) Mutations in dynein link motor neuron degeneration to defects in retrograde transport. Science, 300, 808-812.
49. Xia, C.-H., Roberts, E.A., Her, L.-S., Liu, X., Williams, D.S., Cleveland, D.W. and Goldstein, L.S.B. (2003) Abnormal neurofilament transport caused by targeted disruption of neuronal kinesin heavy chain KIF5A. J. Cell Biol., 161, 55-66.
50. Ferreirinha, F., Quattrini, A., Pirozzi, M., Valsecchi, V., Dina, G., Broccoli, V., Auricchio, A., Piemonte, F., Tozzi, G., Gaeta, L. et al. (2004) Axonal degeneration in paraplegin-deficient mice is associated with abnormal mitochondria and impairment of axonal transport. J. Clin. Invest., 113, 231-242.
51. Kieran, D., Hafezparast, M., Bohnert, S., Dick, J.R., Martin, J., Schiavo, G., Fisher, E.M. and Greensmith, L. (2005) A mutation in dynein rescues axonal transport defects and extends the life span of ALS mice. J. Cell Biol., 169, 561-567.
52. Asano, M., Furukawa, K., Kido, M., Matsumoto, S., Umesaki, Y., Kochibe, N. and Iwakura, Y. (1997) Growth retardation and early death of beta-1,4-galactosyltransferase knockout mice with augmented proliferation and abnormal differentiation of epithelial cells. EMBO J., 16, 1850-1857.
53. Llewellyn-Smith, I.J., Pilowsky, P. and Minson, J.B. (1992) Retrograde tracers for light and electron microscopy. In Bolam, J.P. (ed.), Experimental Neuroanatomy: A Practical Approach. Oxford University Press, New York, pp. 32-59.
54. Duchala, C.S., Shick, H.E., Garcia, J., Deweese, D.M., Sun, X., Stewart, V.J. and Maclin, W.B. (2004) The toppler mouse: A novel mutant exhibiting loss of Purkinje cells. J. Comp. Neurol., 476, 113-129.
55. Zanjani, H., Lemaigre-Dubreuil, Y., Tillakaratnr, N.J., Blokhin, A., McMahon, R.P., Tobin, A.J., Vogel, M.W. and Mariani, J. (2004) Cerebellar Purkinje cell loss in aging Hu-Bcl-2 transgenic mice. J. Comp. Neurol., 475, 481-492.
56. Shefner, J.M., Jillapalli, D. and Bradshaw, D.Y. (1999) Reducing intersubject variability in motor unit number estimation. Muscle Nerve, 22, 1457-1460.