A large scale huntingtin protein interaction network implicates RHO GTPase signaling pathways in huntington disease

Journal of Biological Chemistry

Volumn 289, Issue 10, 2014, Pages 6709-6726

  Tourette, Cendrine ^a   Li, Biao ^a   Bell, Russell ^b,c   O'Hare, Shannon ^a   Kaltenbach, Linda S ^b,d   Mooney, Sean D ^a   Hughes, Robert E ^a  

^a BUCK INSTITUTE FOR RESEARCH ON AGING   (United States)

^b Prolexys Pharmaceuticals   (United States)

^c UNIVERSITY OF UTAH   (United States)

^d DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEINS;

HUNTINGTIN; HUNTINGTON DISEASE; INTERACTION NETWORKS; NEUROPSYCHIATRIC DISORDER; PROTEIN INTERACTION NETWORKS; SIGNALING PATHWAYS;

ACTIVE NETWORKS;

BRAIN PROTEIN; BRAIN SPECIFIC ANGIOGENESIS INHIBITOR 1 ASSOCIATED PROTEIN 2; EZRIN; HUNTINGTIN; MAMMALIAN TARGET OF RAPAMYCIN; P21 ACTIVATED KINASE 2; PHOSPHATIDYLINOSITOL 3 KINASE; RAC1 PROTEIN; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; UNCLASSIFIED DRUG;

ARTICLE; CELLULAR DISTRIBUTION; COMPLEX FORMATION; CONTROLLED STUDY; FILOPODIUM; HUMAN; HUMAN CELL; HUNTINGTON CHOREA; INTRACELLULAR SIGNALING; NEUROPATHOLOGY; NEUROTOXICITY; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION;

CELL DEATH; CELL MOTILITY; COMPUTATIONAL BIOLOGY; HUNTINGTON DISEASE; NEURODEGENERATION; NEURODEGENERATIVE DISEASES; PROTEIN-PROTEIN INTERACTIONS; PROTEOMICS; RHO GTPASES;

ANIMALS; HEK293 CELLS; HUMANS; HUNTINGTON DISEASE; METABOLIC NETWORKS AND PATHWAYS; MICE; NERVE TISSUE PROTEINS; NIH 3T3 CELLS; PSEUDOPODIA; RHO GTP-BINDING PROTEINS;

EID: 84896790519     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M113.523696     Document Type: Article

References (92)

1. The 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
2. Reiner, A., Albin, R. L., Anderson, K. D., D'Amato, C. J., Penney, J. B., and Young, A. B. (1988) Differential loss of striatal projection neurons in Huntington disease. Proc. Natl. Acad. Sci. U.S.A. 85, 5733-5737
3. Walker, F. O. (2007) Huntington's disease. Lancet 369, 218-228
4. Borrell-Pagès, M., Zala, D., Humbert, S., and Saudou, F. (2006) Huntington's disease: from huntingtin function and dysfunction to therapeutic strategies. Cell. Mol. Life Sci. 63, 2642-2660
5. Zuccato, C., Valenza, M., and Cattaneo, E. (2010) Molecular mechanisms and potential therapeutical targets in Huntington's disease. Physiol. Rev. 90, 905-981
6. Wellington, C. L., Ellerby, L. M., Gutekunst, C. A., Rogers, D., Warby, S., Graham, R. K., Loubser, O., van Raamsdonk, J., Singaraja, R., Yang, Y. Z., Gafni, J., Bredesen, D., Hersch, S. M., Leavitt, B. R., Roy, S., Nicholson, D. W., and Hayden, M. R. (2002) Caspase cleavage of mutant huntingtin precedes neurodegeneration in Huntington's disease. J. Neurosci. 22, 7862-7872
7. Graham, R. K., Deng, Y., Slow, E. J., Haigh, B., Bissada, N., Lu, G., Pearson, J., Shehadeh, J., Bertram, L., Murphy, Z., Warby, S. C., Doty, C. N., Roy, S., Wellington, C. L., Leavitt, B. R., Raymond, L. A., Nicholson, D. W., and Hayden, M. R. (2006) Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin. Cell 125, 1179-1191
8. Ratovitski, T., Gucek, M., Jiang, H., Chighladze, E., Waldron, E., D'Ambola, J., Hou, Z., Liang, Y., Poirier, M. A., Hirschhorn, R. R., Graham, R., Hayden, M. R., Cole, R. N., and Ross, C. A. (2009) Mutant huntingtin N-terminal fragments of specific size mediate aggregation and toxicity in neuronal cells. J. Biol. Chem. 284, 10855-10867
9. Sun, B., Fan, W., Balciunas, A., Cooper, J. K., Bitan, G., Steavenson, S., Denis, P. E., Young, Y., Adler, B., Daugherty, L., Manoukian, R., Elliott, G., Shen, W., Talvenheimo, J., Teplow, D. B., Haniu, M., Haldankar, R., Wypych, J., Ross, C. A., Citron, M., and Richards, W. G. (2002) Polyglutamine repeat length-dependent proteolysis of huntingtin. Neurobiol. Dis. 11, 111-122
10. 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
11. Holbert, S., Denghien, I., Kiechle, T., Rosenblatt, A., Wellington, C., Hayden, M. R., Margolis, R. L., Ross, C. A., Dausset, J., Ferrante, R. J., and Néri, C. (2001) The Gln-Ala repeat transcriptional activator CA150 interacts with huntingtin: neuropathologic and genetic evidence for a role in Huntington's disease pathogenesis. Proc. Natl. Acad. Sci. U.S.A. 98, 1811-1816
12. Steffan, J. S., Kazantsev, A., Spasic-Boskovic, O., Greenwald, M., Zhu, Y. Z., Gohler, H., Wanker, E. E., Bates, G. P., Housman, D. E., and Thompson, L. M. (2000) The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc. Natl. Acad. Sci. U.S.A. 97, 6763-6768
13. Caviston, J. P., Ross, J. L., Antony, S. M., Tokito, M., and Holzbaur, E. L. (2007) Huntingtin facilitates dynein/dynactin-mediated vesicle transport. Proc. Natl. Acad. Sci. U.S.A. 104, 10045-10050
14. Culver, B. P., Savas, J. N., Park, S. K., Choi, J. H., Zheng, S., Zeitlin, S. O., Yates, J. R., 3rd, and Tanese, N. (2012) Proteomic analysis of wild-type and mutant huntingtin-associated proteins in mouse brains identifies unique interactions and involvement in protein synthesis. J. Biol. Chem. 287, 21599-21614
15. Goehler, H., Lalowski, M., Stelzl, U., Waelter, S., Stroedicke, M., Worm, U., Droege, A., Lindenberg, K. S., Knoblich, M., Haenig, C., Herbst, M., Suopanki, J., Scherzinger, E., Abraham, C., Bauer, B., Hasenbank, R., Fritzsche, A., Ludewig, A. H., Büssow, K., Buessow, K., Coleman, S. H., Gutekunst, C. A., Landwehrmeyer, B. G., Lehrach, H., and Wanker, E. E. (2004) A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease. Mol. Cell 15, 853-865
16. Kaltenbach, L. S., Romero, E., Becklin, R. R., Chettier, R., Bell, R., Phansalkar, A., Strand, A., Torcassi, C., Savage, J., Hurlburt, A., Cha, G. H., Ukani, L., Chepanoske, C. L., Zhen, Y., Sahasrabudhe, S., Olson, J., Kurschner, C., Ellerby, L. M., Peltier, J. M., Botas, J., and Hughes, R. E. (2007) Huntingtin interacting proteins are genetic modifiers of neurodegeneration. PLoS Genet. 3, e82
17. Shirasaki, D. I., Greiner, E. R., Al-Ramahi, I., Gray, M., Boontheung, P., Geschwind, D. H., Botas, J., Coppola, G., Horvath, S., Loo, J. A., and Yang, X. W. (2012) Network organization of the huntingtin proteomic interactome in mammalian brain. Neuron 75, 41-57
18. Bell, R., Hubbard, A., Chettier, R., Chen, D., Miller, J. P., Kapahi, P., Tarnopolsky, M., Sahasrabuhde, S., Melov, S., and Hughes, R. E. (2009) A human protein interaction network shows conservation of aging processes between human and invertebrate species. PLoS Genet. 5, e1000414
19. Bandyopadhyay, S., Chiang, C. Y., Srivastava, J., Gersten, M., White, S., Bell, R., Kurschner, C., Martin, C., Smoot, M., Sahasrabudhe, S., Barber, D. L., Chanda, S. K., and Ideker, T. (2010) A human MAP kinase interactome. Nat. Methods 7, 801-805
20. Ge, H., Walhout, A. J., and Vidal, M. (2003) Integrating 'omic' information: a bridge between genomics and systems biology. Trends Genet. 19, 551-560
21. LaCount, D. J., Vignali, M., Chettier, R., Phansalkar, A., Bell, R., Hesselberth, J. R., Schoenfeld, L. W., Ota, I., Sahasrabudhe, S., Kurschner, C., Fields, S., and Hughes, R. E. (2005) A protein interaction network of the malaria parasite Plasmodium falciparum. Nature 438, 103-107
22. Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., Amin, N., Schwikowski, B., and Ideker, T. (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498-2504
23. Keshava Prasad, T. S., Goel, R., Kandasamy, K., Keerthikumar, S., Kumar, S., Mathivanan, S., Telikicherla, D., Raju, R., Shafreen, B., Venugopal, A., Balakrishnan, L., Marimuthu, A., Banerjee, S., Somanathan, D. S., Sebastian, A., Rani, S., Ray, S., Harrys Kishore, C. J., Kanth, S., Ahmed, M., Kashyap, M. K., Mohmood, R., Ramachandra, Y. L., Krishna, V., Rahiman, B. A., Mohan, S., Ranganathan, P., Ramabadran, S., Chaerkady, R., and Pandey, A. (2009) Human Protein Reference Database-2009 update. Nucleic Acids Res. 37, D767-D772
24. Hodges, A., Strand, A. D., Aragaki, A. K., Kuhn, A., Sengstag, T., Hughes, G., Elliston, L. A., Hartog, C., Goldstein, D. R., Thu, D., Hollingsworth, Z. R., Collin, F., Synek, B., Holmans, P. A., Young, A. B., Wexler, N. S., Delorenzi, M., Kooperberg, C., Augood, S. J., Faull, R. L., Olson, J. M., Jones, L., and Luthi-Carter, R. (2006) Regional and cellular gene expression changes in human Huntington's disease brain. Hum. Mol. Genet. 15, 965-977
25. Kuhn, A., Goldstein, D. R., Hodges, A., Strand, A. D., Sengstag, T., Kooperberg, C., Becanovic, K., Pouladi, M. A., Sathasivam, K., Cha, J. H., Hannan, A. J., Hayden, M. R., Leavitt, B. R., Dunnett, S. B., Ferrante, R. J., Albin, R., Shelbourne, P., Delorenzi, M., Augood, S. J., Faull, R. L., Olson, J. M., Bates, G. P., Jones, L., and Luthi-Carter, R. (2007) Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage. Hum. Mol. Genet. 16, 1845-1861
26. Miller, J. P., Yates, B. E., Al-Ramahi, I., Berman, A. E., Sanhueza, M., Kim, E., de Haro, M., DeGiacomo, F., Torcassi, C., Holcomb, J., Gafni, J., Mooney, S. D., Botas, J., Ellerby, L. M., and Hughes, R. E. (2012)Agenomescale RNA-interference screen identifies RRAS signaling as a pathologic feature of Huntington's disease. PLoS Genet. 8, e1003042
27. Campeau, E., Ruhl, V. E., Rodier, F., Smith, C. L., Rahmberg, B. L., Fuss, J. O., Campisi, J., Yaswen, P., Cooper, P. K., and Kaufman, P. D. (2009) A versatile viral system for expression and depletion of proteins in mammalian cells. PLoS One 4, e6529
28. Miller, J. P., Holcomb, J., Al-Ramahi, I., de Haro, M., Gafni, J., Zhang, N., Kim, E., Sanhueza, M., Torcassi, C., Kwak, S., Botas, J., Hughes, R. E., and Ellerby, L. M. (2010) Matrix metalloproteinases are modifiers of huntingtin proteolysis and toxicity in Huntington's disease. Neuron 67, 199-212
29. Trettel, F., Rigamonti, D., Hilditch-Maguire, P., Wheeler, V. C., Sharp, A. H., Persichetti, F., Cattaneo, E., and MacDonald, M. E. (2000) Dominant phenotypes produced by the HD mutation in STHdh(Q111) striatal cells. Hum. Mol. Genet. 9, 2799-2809
30. Barabási, A. L., Gulbahce, N., and Loscalzo, J. (2011) Network medicine: a network-based approach to human disease. Nat. Rev. Genet. 12, 56-68
31. Yuan, T. L., and Cantley, L. C. (2008) PI3K pathway alterations in cancer: variations on a theme. Oncogene 27, 5497-5510
32. Rommel, C., Camps, M., and Ji, H. (2007) PI3K+ and PI3K+: partners in crime in inflammation in rheumatoid arthritis and beyond? Nat. Rev. Immunol. 7, 191-201
33. Lee, J. Y., Kim, Y. R., Park, J., and Kim, S. (2012) Inositol polyphosphate multikinase signaling in the regulation of metabolism. Ann. N.Y. Acad. Sci. 1271, 68-74
34. Chong, Z. Z., Shang, Y. C., Wang, S., and Maiese, K. (2012)Acritical kinase cascade in neurological disorders: PI 3-K, Akt, and mTOR. Future Neurol. 7, 733-748
35. Ravikumar, B., Vacher, C., Berger, Z., Davies, J. E., Luo, S., Oroz, L. G., Scaravilli, F., Easton, D. F., Duden, R., O'Kane, C. J., and Rubinsztein, D. C. (2004) Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat. Genet. 36, 585-595
36. Seredenina, T., and Luthi-Carter, R. (2012) What have we learned from gene expression profiles in Huntington's disease? Neurobiol. Dis. 45, 83-98
37. Borgonovo, J. E., Troncoso, M., Lucas, J. J., and Sosa, M. A. (2013) Mutant huntingtin affects endocytosis in striatal cells by altering the binding of AP-2 to membranes. Exp. Neurol. 241, 75-83
38. Trushina, E., Singh, R. D., Dyer, R. B., Cao, S., Shah, V. H., Parton, R. G., Pagano, R. E., and McMurray, C. T. (2006) Mutant huntingtin inhibits clathrin-independent endocytosis and causes accumulation of cholesterol in vitro and in vivo. Hum. Mol. Genet. 15, 3578-3591
39. Lange, A., Wickström, S. A., Jakobson, M., Zent, R., Sainio, K., and Fässler, R. (2009) Integrin-linked kinase is an adaptor with essential functions during mouse development. Nature 461, 1002-1006
40. Qin, J., and Wu, C. (2012) ILK: a pseudokinase in the center stage of cell-matrix adhesion and signaling. Curr. Opin. Cell Biol. 24, 607-613
41. Bauer, P. O., Wong, H. K., Oyama, F., Goswami, A., Okuno, M., Kino, Y., Miyazaki, H., and Nukina, N. (2009) Inhibition of Rho kinases enhances the degradation of mutant huntingtin. J. Biol. Chem. 284, 13153-13164
42. Shao, J., Welch, W. J., and Diamond, M. I. (2008) ROCK and PRK-2 mediate the inhibitory effect of Y-27632 on polyglutamine aggregation. FEBS Lett. 582, 1637-1642
43. De Las Rivas, J., and Fontanillo, C. (2010) Protein-protein interactions essentials: key concepts to building and analyzing interactome networks. PLoS Comput. Biol. 6, e1000807
44. Buchsbaum, R. J. (2007) Rho activation at a glance. J. Cell Sci. 120, 1149-1152
45. Miki, H., Yamaguchi, H., Suetsugu, S., and Takenawa, T. (2000) IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling. Nature 408, 732-735
46. Mattila, P. K., Pykäläinen, A., Saarikangas, J., Paavilainen, V. O., Vihinen, H., Jokitalo, E., and Lappalainen, P. (2007) Missing-in-metastasis and IRSp53 deform PI(4,5)P2-rich membranes by an inverse BAR domain-like mechanism. J. Cell Biol. 176, 953-964
47. Robens, J. M., Yeow-Fong, L., Ng, E., Hall, C., and Manser, E. (2010) Regulation of IRSp53-dependent filopodial dynamics by antagonism between 14-3-3 binding and SH3-mediated localization. Mol. Cell. Biol. 30, 829-844
48. Neisch, A. L., and Fehon, R. G. (2011) Ezrin, Radixin and Moesin: key regulators of membrane-cortex interactions and signaling. Curr. Opin. Cell Biol. 23, 377-382
49. Marsick, B. M., Roche, F. K., and Letourneau, P. C. (2012) Repulsive axon guidance cues ephrin-A2 and slit3 stop protrusion of the growth cone leading margin concurrently with inhibition of ADF/cofilin andERMproteins. Cytoskeleton 69, 496-505
50. Marchler-Bauer, A., Lu, S., Anderson, J. B., Chitsaz, F., Derbyshire, M. K., DeWeese-Scott, C., Fong, J. H., Geer, L. Y., Geer, R. C., Gonzales, N. R., Gwadz, M., Hurwitz, D. I., Jackson, J. D., Ke, Z., Lanczycki, C. J., Lu, F., Marchler, G. H., Mullokandov, M., Omelchenko, M. V., Robertson, C. L., Song, J. S., Thanki, N., Yamashita, R. A., Zhang, D., Zhang, N., Zheng, C., and Bryant, S. H. (2011) CDD: a conserved domain database for the functional annotation of proteins. Nucleic Acids Res. 39, D225-D229
51. Bedford, M. T., Reed, R., and Leder, P. (1998) WW domain-mediated interactions reveal a spliceosome-associated protein that binds a third class of proline-rich motif: the proline glycine and methionine-rich motif. Proc. Natl. Acad. Sci. U.S.A. 95, 10602-10607
52. Chow, W. N., Luk, H. W., Chan, H. Y., and Lau, K. F. (2012) Degradation of mutant huntingtin via the ubiquitin/proteasome system is modulated by FE65. Biochem. J. 443, 681-689
53. Faber, P. W., Barnes, G. T., Srinidhi, J., Chen, J., Gusella, J. F., and Mac-Donald, M. E. (1998) Huntingtin interacts with a family of WW domain proteins. Hum. Mol. Genet. 7, 1463-1474
54. Passani, L. A., Bedford, M. T., Faber, P. W., McGinnis, K. M., Sharp, A. H., Gusella, J. F., Vonsattel, J. P., and MacDonald, M. E. (2000) Huntingtin's WW domain partners in Huntington's disease post-mortem brain fulfill genetic criteria for direct involvement in Huntington's disease pathogenesis. Hum. Mol. Genet. 9, 2175-2182
55. Jiang, Y. J., Che, M. X., Yuan, J. Q., Xie, Y. Y., Yan, X. Z., and Hu, H. Y. (2011) Interaction with polyglutamine-expanded huntingtin alters cellular distribution and RNA processing of huntingtin yeast two-hybrid protein A (HYPA). J. Biol. Chem. 286, 25236-25245
56. Zheng, S., Ghitani, N., Blackburn, J. S., Liu, J. P., and Zeitlin, S. O. (2012) A series of N-terminal epitope tagged Hdh knock-in alleles expressing normal and mutant huntingtin: their application to understanding the effect of increasing the length of normal Huntingtin's polyglutamine stretch on CAG140 mouse model pathogenesis. Mol. Brain 5, 28
57. Allen, M., Friedler, A., Schon, O., and Bycroft, M. (2002) The structure of an FF domain from human HYPA/FBP11. J. Mol. Biol. 323, 411-416
58. Bedford, M. T., and Leder, P. (1999) The FF domain: a novel motif that often accompaniesWWdomains. Trends Biochem. Sci. 24, 264-265
59. Chiang, M. C., Chen, C. M., Lee, M. R., Chen, H. W., Chen, H. M., Wu, Y. S., Hung, C. H., Kang, J. J., Chang, C. P., Chang, C., Wu, Y. R., Tsai, Y. S., and Chern, Y. (2010) Modulation of energy deficiency in Huntington's disease via activation of the peroxisome proliferator-activated receptor. Hum. Mol. Genet. 19, 4043-4058
60. Huang, H., Li, L., Wu, C., Schibli, D., Colwill, K., Ma, S., Li, C., Roy, P., Ho, K., Songyang, Z., Pawson, T., Gao, Y., and Li, S. S. (2008) Defining the specificity space of the human SRC homology 2 domain. Mol. Cell. Proteomics 7, 768-784
61. Morton, C. J., and Campbell, I. D. (1994) SH3 domains. Molecular 'Velcro'. Curr. Biol. 4, 615-617
62. Chuang, J. Z., Zhou, H., Zhu, M., Li, S. H., Li, X. J., and Sung, C. H. (2002) Characterization of a brain-enriched chaperone, MRJ, that inhibits Huntingtin aggregation and toxicity independently. J. Biol. Chem. 277, 19831-19838
63. Lu, B., Al-Ramahi, I., Valencia, A., Wang, Q., Berenshteyn, F., Yang, H., Gallego-Flores, T., Ichcho, S., Lacoste, A., Hild, M., Difiglia, M., Botas, J., and Palacino, J. (2013) Identification of NUB1 as a suppressor of mutant Huntington toxicity via enhanced protein clearance. Nat. Neurosci. 16, 562-570
64. Muchowski, P. J., Schaffar, G., Sittler, A., Wanker, E. E., Hayer-Hartl, M. K., and Hartl, F. U. (2000) Hsp70 and hsp40 chaperones can inhibit self-assembly of polyglutamine proteins into amyloid-like fibrils. Proc. Natl. Acad. Sci. U.S.A. 97, 7841-7846
65. Suetsugu, S., Toyooka, K., and Senju, Y. (2010) Subcellular membrane curvature mediated by the BAR domain superfamily proteins. Semin. Cell Dev. Biol. 21, 340-349
66. Disanza, A., Mantoani, S., Hertzog, M., Gerboth, S., Frittoli, E., Steffen, A., Berhoerster, K., Kreienkamp, H. J., Milanesi, F., Di Fiore, P. P., Ciliberto, A., Stradal, T. E., and Scita, G. (2006) Regulation of cell shape by Cdc42 is mediated by the synergic actin-bundling activity of the Eps8-IRSp53 complex. Nat. Cell Biol. 8, 1337-1347
67. Krugmann, S., Jordens, I., Gevaert, K., Driessens, M., Vandekerckhove, J., and Hall, A. (2001) Cdc42 induces filopodia by promoting the formation of an IRSp53:Mena complex. Curr. Biol. 11, 1645-1655
68. Lim, K. B., Bu, W., Goh, W. I., Koh, E., Ong, S. H., Pawson, T., Sudhaharan, T., and Ahmed, S. (2008) The Cdc42 effector IRSp53 generates filopodia by coupling membrane protrusion with actin dynamics. J. Biol. Chem. 283, 20454-20472
69. Nakagawa, H., Miki, H., Nozumi, M., Takenawa, T., Miyamoto, S., Wehland, J., and Small, J. V. (2003) IRSp53 is colocalised with WAVE2 at the tips of protruding lamellipodia and filopodia independently of Mena. J. Cell Sci. 116, 2577-2583
70. Suetsugu, S., Murayama, K., Sakamoto, A., Hanawa-Suetsugu, K., Seto, A., Oikawa, T., Mishima, C., Shirouzu, M., Takenawa, T., and Yokoyama, S. (2006) The RAC binding domain/IRSp53-MIM homology domain of IRSp53 induces RAC-dependent membrane deformation. J. Biol. Chem. 281, 35347-35358
71. Li, S. H., and Li, X. J. (2004) Huntingtin-protein interactions and the pathogenesis of Huntington's disease. Trends Genet. 20, 146-154
72. Jiang, H., Poirier, M. A., Liang, Y., Pei, Z., Weiskittel, C. E., Smith, W. W., DeFranco, D. B., and Ross, C. A. (2006) Depletion of CBP is directly linked with cellular toxicity caused by mutant huntingtin. Neurobiol. Dis. 23, 543-551
73. Yu, Z., Zhou, D., Cheng, G., and Mattson, M. P. (2000) Neuroprotective role for the p50 subunit of NFB in an experimental model of Huntington's disease. J. Mol. Neurosci. 15, 31-44
74. Manser, E., Leung, T., Salihuddin, H., Zhao, Z. S., and Lim, L. (1994) A brain serine/threonine protein kinase activated by Cdc42 and Rac1. Nature 367, 40-46
75. Mattila, P. K., and Lappalainen, P. (2008) Filopodia: molecular architecture and cellular functions. Nat. Rev. Mol. Cell Biol. 9, 446-454
76. Galbraith, C. G., Yamada, K. M., and Galbraith, J. A. (2007) Polymerizing actin fibers position integrins primed to probe for adhesion sites. Science 315, 992-995
77. Vasioukhin, V., Bauer, C., Yin, M., and Fuchs, E. (2000) Directed actin polymerization is the driving force for epithelial cell-cell adhesion. Cell 100, 209-219
78. Dent, E. W., Kwiatkowski, A. V., Mebane, L. M., Philippar, U., Barzik, M., Rubinson, D. A., Gupton, S., Van Veen, J. E., Furman, C., Zhang, J., Alberts, A. S., Mori, S., and Gertler, F. B. (2007) Filopodia are required for cortical neurite initiation. Nat. Cell Biol. 9, 1347-1359
79. Kwiatkowski, A. V., Rubinson, D. A., Dent, E. W., Edward van Veen, J., Leslie, J. D., Zhang, J., Mebane, L. M., Philippar, U., Pinheiro, E. M., Burds, A. A., Bronson, R. T., Mori, S., Fässler, R., and Gertler, F. B. (2007) Ena/ VASP is Required for neuritogenesis in the developing cortex. Neuron 56, 441-455
80. Menna, E., Fossati, G., Scita, G., and Matteoli, M. (2011) From filopodia to synapses: the role of actin-capping and anti-capping proteins. Eur. J. Neurosci. 34, 1655-1662
81. Spillane, M., Ketschek, A., Donnelly, C. J., Pacheco, A., Twiss, J. L., and Gallo, G. (2012) Nerve growth factor-induced formation of axonal filopodia and collateral branches involves the intra-axonal synthesis of regulators of the actin-nucleating Arp2/3 complex. J. Neurosci. 32, 17671-17689
82. Millard, T. H., Bompard, G., Heung, M. Y., Dafforn, T. R., Scott, D. J., Machesky, L. M., and Fütterer, K. (2005) Structural basis of filopodia formation induced by the IRSp53/MIM homology domain of human IRSp53. EMBO J. 24, 240-250
83. Ngounou Wetie, A. G., Sokolowska, I., Woods, A. G., Roy, U., Deinhardt, K., and Darie, C. C. (2013) Protein-protein interactions: switch from classical methods to proteomics and bioinformatics-based approaches. Cell. Mol. Life Sci. 71, 205-228
84. Schaefer, M. H., Wanker, E. E., and Andrade-Navarro, M. A. (2012) Evolution and function of CAG/polyglutamine repeats in protein-protein interaction networks. Nucleic Acids Res. 40, 4273-4287
85. Southwell, A. L., Khoshnan, A., Dunn, D. E., Bugg, C. W., Lo, D. C., and Patterson, P. H. (2008) Intrabodies binding the proline-rich domains of mutant huntingtin increase its turnover and reduce neurotoxicity. J. Neurosci. 28, 9013-9020
86. Neveklovska, M., Clabough, E. B., Steffan, J. S., and Zeitlin, S. O. (2012) Deletion of the huntingtin proline-rich region does not significantly affect normal huntingtin function in mice. J. Huntingtons Dis. 1, 71-87
87. Ahmed, S., Goh, W. I., and Bu, W. (2010) I-BAR domains, IRSp53 and filopodium formation. Semin. Cell Dev. Biol. 21, 350-356
88. Hori, K., Yasuda, H., Konno, D., Maruoka, H., Tsumoto, T., and Sobue, K. (2005) NMDA receptor-dependent synaptic translocation of insulin receptor substrate p53 via protein kinase C signaling. J. Neurosci. 25, 2670-2681
89. Soltau, M., Berhörster, K., Kindler, S., Buck, F., Richter, D., and Kreienkamp, H. J. (2004) Insulin receptor substrate of 53 kDa links postsynaptic shank to PSD-95. J. Neurochem. 90, 659-665
90. Thomas, E. A., Foye, P. E., Alvarez, C. E., Usui, H., and Sutcliffe, J. G. (2001) Insulin receptor substrate protein p53 localization in rats suggests mechanism for specific polyglutamine neurodegeneration. Neurosci. Lett. 309, 145-148
91. Ferrante, R. J., Kowall, N. W., and Richardson, E. P., Jr. (1991) Proliferative and degenerative changes in striatal spiny neurons in Huntington's disease: a combined study using the section-Golgi method and calbindin D28k immunocytochemistry. J. Neurosci. 11, 3877-3887
92. Graveland, G. A., Williams, R. S., and DiFiglia, M. (1985) Evidence for degenerative and regenerative changes in neostriatal spiny neurons in Huntington's disease. Science 227, 770-773