To the Nucleus with Proteomics

  • Bryen A. Jordan
  • Edward B. Ziff


In this chapter we review proteomic studies performed on purified postsynaptic density (PSD) fractions and analyze what their results reveal about nuclear signaling. Overall, these studies show that PSDs are similar to the cytoplasmic protein complexes found at other intercellular junctions. We find that PSDs contain numerous calmodulin (CAM)-associated transcriptional coactivators, nucleocytoplasmic shuttling proteins that bind RNA and potential splicing factors. Moreover, in conjunction with bioinformatics, we identify novel nucleocytoplasmic shuttling proteins at synapses. These results strongly suggest that control of the spatial distribution of synapse-associated nuclear factors regulates nuclear function.


NMDA Receptor Dendritic Spine Splice Factor Postsynaptic Density Cajal Body 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aplin, A. E., and Juliano, R. L. (2001) Regulation of nucleocytoplasmic trafficking by cell adhesion receptors and the cytoskeleton. J. Cell Biol. 155, 187–191.PubMedGoogle Scholar
  2. Ataman, B., Ashley, J., Gorczyca, D., Gorczyca, M., Mathew, D., Wichmann, C., Sigrist, S. J., and Budnik, V. (2006) Nuclear trafficking of Drosophila Frizzled-2 during synapse development requires the PDZ protein dGRIP. Proc. Natl. Acad. Sci. USA 103, 7841–7846.Google Scholar
  3. Balda, M. S., and Matter, K. (2000) The tight junction protein ZO-1 and an interacting tran scription factor regulate ErbB-2 expression. EMBO J. 19, 2024–2033.PubMedGoogle Scholar
  4. Banker, G., Churchill, L., and Cotman, C. W. (1974) Proteins of the postsynaptic density. J. Cell Biol. 63, 456–465.PubMedGoogle Scholar
  5. Beesley, P. W., Mummery, R., and Tibaldi, J. (1995) N-cadherin is a major glycoprotein component of isolated rat forebrain postsynaptic densities. J. Neurochem. 64, 2288–2294.PubMedGoogle Scholar
  6. Beffert, U., Weeber, E. J., Durudas, A., Qiu, S., Masiulis, I., Sweatt, J. D., Li, W. P., Adel mann, G., Frotscher, M., Hammer, R. E., and Herz, J. (2005) Modulation of synaptic plasticity and memory by Reelin involves differential splicing of the lipoprotein receptor ApoEr2. Neuron 47, 567–579.PubMedGoogle Scholar
  7. Bianchi, E., Denti, S., Granata, A., Bossi, G., Geginat, J., Villa, A., Rogge, L., and Pardi, R. (2000) Integrin LFA-1 interacts with the transcriptional co-activator JAB1 to modulate AP-1 activity. Nature 404, 617–621.PubMedGoogle Scholar
  8. Black, D. L., and Graveley, B. R. (2006) Splicing bioinformatics to biology. Genome Biol. 7, 317.PubMedGoogle Scholar
  9. Blaustein, M., Pelisch, F., Tanos, T., Munoz, M. J., Wengier, D., Quadrana, L., Sanford, J. R., Muschietti, J. P., Kornblihtt, A. R., Caceres, J. F., et al. (2005) Concerted regulation of nuclear and cytoplasmic activities of SR proteins by AKT. Nat. Struct. Mol. Biol. 12, 1037–1044.PubMedGoogle Scholar
  10. Butz, S., and Kemler, R. (1994) Distinct cadherin-catenin complexes in Ca(2+)-dependent cell-cell adhesion. FEBS Lett. 355, 195–200.PubMedGoogle Scholar
  11. Cao, X., and Sudhof, T. C. (2001) A transcriptionally active complex of APP with Fe65 and histone acetyltransferase Tip60. Science 293, 115–120.PubMedGoogle Scholar
  12. Carlin, R. K., Grab, D. J., Cohen, R. S., and Siekevitz, P. (1980) Isolation and characteriza tion of postsynaptic densities from various brain regions: enrichment of different types of postsynaptic densities. J. Cell Biol. 86, 831–845.PubMedGoogle Scholar
  13. Chakraborty, S., Reineke, E. L., Lam, M., Li, X., Liu, Y., Gao, C., Khurana, S., and Kao, H. Y. (2006)α-Actinin 4 Potentiates Myocyte Enhancer Factor-2 Transcription Activ ity by Antagonizing Histone Deacetylase 7. J. Biol. Chem. 281, 35070–35080.PubMedGoogle Scholar
  14. Chan, C. S., Weeber, E. J., Kurup, S., Sweatt, J. D., and Davis, R. L. (2003) Integrin require ment for hippocampal synaptic plasticity and spatial memory. J. Neurosci. 23, 7107–7116.PubMedGoogle Scholar
  15. Chawla, S., Vanhoutte, P., Arnold, F. J., Huang, C. L., and Bading, H. (2003) Neuronal activ ity-dependent nucleocytoplasmic shuttling of HDAC4 and HDAC5. J. Neurochem. 85, 151–159.PubMedGoogle Scholar
  16. Chen, J. T., Lu, D. H., Chia, C. P., Ruan, D. Y., Sabapathy, K., and Xiao, Z. C. (2005) Im paired long-term potentiation in c-Jun N-terminal kinase 2-deficient mice. J. Neurochem. 93, 463–473.PubMedGoogle Scholar
  17. Chih, B., Gollan, L., and Scheiffele, P. (2006) Alternative splicing controls selective trans- synaptic interactions of the neuroligin-neurexin complex. Neuron 51, 171–178.PubMedGoogle Scholar
  18. Chung, H. J., Xia, J., Scannevin, R. H., Zhang, X., and Huganir, R. L. (2000) Phosphorylation of the AMPA receptor subunit GluR2 differentially regulates its interaction with PDZ domain-containing proteins. J. Neurosci. 20, 7258–7267.PubMedGoogle Scholar
  19. Cioce, M., and Lamond, A. I. (2005) CAJAL BODIES: A Long History of Discovery. Annu. Rev. Cell Dev. Biol. 21, 105–131.PubMedGoogle Scholar
  20. Cohen, R. S., Blomberg, F., Berzins, K., and Siekevitz, P. (1977) The structure of postsynap tic densities isolated from dog cerebral cortex. I. Overall morphology and protein com position. J. Cell Biol. 74, 181–203.Google Scholar
  21. Collins, M. O., Husi, H., Yu, L., Brandon, J. M., Anderson, C. N., Blackstock, W. P., Choudhary, J. S., and Grant, S. G. (2006) Molecular characterization and comparison of the components and multiprotein complexes in the postsynaptic proteome. J. Neurochem. 97 Suppl 1, 16–23.Google Scholar
  22. Consortium, I. H. G. S. (2004) Finishing the euchromatic sequence of the human genome. Nature 431, 931–945.Google Scholar
  23. Cyert, M. S. (2001) Regulation of nuclear localization during signaling. J. Biol. Chem. 276, 20805–20808.PubMedGoogle Scholar
  24. D’Arcangelo, G., Miao, G. G., Chen, S. C., Soares, H. D., Morgan, J. I., and Curran, T. (1995) A rotein related to extracellular matrix proteins deleted in the mouse mutant reeler. Nature 374, 719–723.PubMedGoogle Scholar
  25. Deisseroth, K., Mermelstein, P. G., Xia, H., and Tsien, R. W. (2003) Signaling from synapse to nucleus: the logic behind the mechanisms. Curr. Opin. Neurobiol. 13, 354–365.PubMedGoogle Scholar
  26. Dosemeci, A., Tao-Cheng, J. H., Vinade, L., and Jaffe, H. (2006) Preparation of postsynaptic density fraction from hippocampal slices and proteomic analysis. Biochem. Biophys. Res. Commun. 339, 687–694.PubMedGoogle Scholar
  27. Dye, B. T., and Patton, J. G. (2001) An RNA recognition motif (RRM) is required for the localization of PTB-associated splicing factor (PSF) to subnuclear speckles. Exp. Cell Res. 263, 131–144.PubMedGoogle Scholar
  28. Fagotto, F., Funayama, N., Gluck, U., and Gumbiner, B. M. (1996) Binding to cadherins antagonizes the signaling activity of beta-catenin during axis formation in Xenopus. J. Cell Biol. 132, 1105–1114.PubMedGoogle Scholar
  29. Feng, Y., Gutekunst, C. A., Eberhart, D. E., Yi, H., Warren, S. T., and Hersch, S. M. (1997) Fragile X mental retardation protein: nucleocytoplasmic shuttling and association with somatodendritic ribosomes. J. Neurosci. 17, 1539–1547.PubMedGoogle Scholar
  30. Flavell, S. W., Cowan, C. W., Kim, T. K., Greer, P. L., Lin, Y., Paradis, S., Griffith, E. C., Hu, L. S., Chen, C., and Greenberg, M. E. (2006) Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science 311, 1008–1012.PubMedGoogle Scholar
  31. Fu, X., McGrath, S., Pasillas, M., Nakazawa, S., and Kamps, M. P. (1999) EB-1, a tyrosine kinase signal transduction gene, is transcriptionally activated in the t(1;19) subset of pre-B ALL, which express oncoprotein E2a-Pbx1. Oncogene 18, 4920–4929.PubMedGoogle Scholar
  32. Fujii, R., Okabe, S., Urushido, T., Inoue, K., Yoshimura, A., Tachibana, T., Nishikawa, T., Hicks, G. G., and Takumi, T. (2005) The RNA binding protein TLS is translocated to dendritic spines by mGluR5 activation and regulates spine morphology. Curr. Biol. 15, 587–593.PubMedGoogle Scholar
  33. Fujii, R., and Takumi, T. (2005) TLS facilitates transport of mRNA encoding an actin-stabilizing protein to dendritic spines. J. Cell Sci. 118, 5755–5765.PubMedGoogle Scholar
  34. Gall, J. G. (2003) The centennial of the Cajal body. Nat. Rev. Mol. Cell Biol. 4, 975–980.PubMedGoogle Scholar
  35. Gama-Carvalho, M., Carvalho, M. P., Kehlenbach, A., Valcarcel, J., and Carmo-Fonseca, M. (2001) Nucleocytoplasmic shuttling of heterodimeric splicing factor U2AF. J. Biol. Chem. 276, 13104–13112.PubMedGoogle Scholar
  36. Gattoni, R., Mahe, D., Mahl, P., Fischer, N., Mattei, M. G., Stevenin, J., and Fuchs, J. P. (1996) The human hnRNP-M proteins: structure and relation with early heat shock- induced splicing arrest and chromosome mapping. Nucleic Acids Res. 24, 2535–2542.PubMedGoogle Scholar
  37. Gerrow, K., and El-Husseini, A. (2006) Cell adhesion molecules at the synapse. Front. Biosci. 11, 2400–2419.PubMedGoogle Scholar
  38. Ghersi, E., Noviello, C., and D’Adamio, L. (2004) Amyloid-beta protein precursor (AbetaPP) intracellular domain-associated protein-1 proteins bind to AbetaPP and modulate its processing in an isoform-specific manner. J. Biol. Chem. 279, 49105–49112.PubMedGoogle Scholar
  39. Gordon, M. D., and Nusse, R. (2006) Wnt signaling: multiple pathways, multiple receptors, and multiple transcription factors. J. Biol. Chem. 281, 22429–22433.PubMedGoogle Scholar
  40. Gorlich, D., and Kutay, U. (1999) Transport between the cell nucleus and the cytoplasm. Annu. Rev. Cell Dev. Biol. 15, 607–660.PubMedGoogle Scholar
  41. Gottardi, C. J., Arpin, M., Fanning, A. S., and Louvard, D. (1996) The junction-associated protein, zonula occludens-1, localizes to the nucleus before the maturation and during the remodeling of cell-cell contacts. Proc. Natl. Acad. Sci. USA 93, 10779–10784.PubMedGoogle Scholar
  42. Graef, I. A., Mermelstein, P. G., Stankunas, K., Neilson, J. R., Deisseroth, K., Tsien, R. W., and Crabtree, G. R. (1999) L-type calcium channels and GSK-3 regulate the activity of NF-ATc4 in hippocampal neurons. Nature 401, 703–708.PubMedGoogle Scholar
  43. Guzowski, J. F., Lyford, G. L., Stevenson, G. D., Houston, F. P., McGaugh, J. L., Worley, P. F., and Barnes, C. A. (2000) Inhibition of activity-dependent arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory. J. Neurosci. 20, 3993–4001.PubMedGoogle Scholar
  44. Hallier, M., Lerga, A., Barnache, S., Tavitian, A., and Moreau-Gachelin, F. (1998) The transcription factor Spi-1/PU.1 interacts with the potential splicing factor TLS. J. Biol. Chem. 273, 4838–4842.PubMedGoogle Scholar
  45. Hardingham, G. E., Arnold, F. J., and Bading, H. (2001) Nuclear calcium signaling controls CREB-mediated gene expression triggered by synaptic activity. Nat. Neurosci. 4, 261–267.PubMedGoogle Scholar
  46. Hatzfeld, M. (2005) The p120 family of cell adhesion molecules. Eur J. Cell Biol. 84, 205–214.PubMedGoogle Scholar
  47. Havik, B., Rokke, H., Bardsen, K., Davanger, S., and Bramham, C. R. (2003) Bursts of high- frequency stimulation trigger rapid delivery of pre-existing alpha-CaMKII mRNA to synapses: a mechanism in dendritic protein synthesis during long-term potentiation in adult awake rats. Eur J. Neurosci. 17, 2679–2689.PubMedGoogle Scholar
  48. Honda, K., Yamada, T., Endo, R., Ino, Y., Gotoh, M., Tsuda, H., Yamada, Y., Chiba, H., and Hirohashi, S. (1998) Actinin-4, a novel actin-bundling protein associated with cell motility and cancer invasion. J. Cell Biol. 140, 1383–1393.PubMedGoogle Scholar
  49. Hsueh, Y. P., and Sheng, M. (1999) Regulated expression and subcellular localization of syndecan heparan sulfate proteoglycans and the syndecan-binding protein CASK/LIN-2 during rat brain development. J. Neurosci. 19, 7415–7425.PubMedGoogle Scholar
  50. Hsueh, Y. P., Wang, T. F., Yang, F. C., and Sheng, M. (2000) Nuclear translocation and tran scription regulation by the membrane-associated guanylate kinase CASK/LIN-2. Nature 404, 298–302.PubMedGoogle Scholar
  51. Huber, K. M., Gallagher, S. M., Warren, S. T., and Bear, M. F. (2002) Altered synaptic plas ticity in a mouse model of fragile X mental retardation. Proc. Natl. Acad. Sci. USA 99, 7746–7750.PubMedGoogle Scholar
  52. Huber, O., Korn, R., McLaughlin, J., Ohsugi, M., Herrmann, B. G., and Kemler, R. (1996) Nuclear localization of beta-catenin by interaction with transcription factor LEF-1. Mech. Dev. 59, 3–10.PubMedGoogle Scholar
  53. Hubner, S., Jans, D. A., and Drenckhahn, D. (2001) Roles of cytoskeletal and junctional plaque proteins in nuclear signaling. Int. Rev. Cytol. 208, 207–265.PubMedGoogle Scholar
  54. Hulsken, J., Birchmeier, W., and Behrens, J. (1994) E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton. J. Cell Biol. 127, 2061–2069.PubMedGoogle Scholar
  55. Husi, H., Ward, M. A., Choudhary, J. S., Blackstock, W. P., and Grant, S. G. (2000) Proteo mic analysis of NMDA receptor-adhesion protein signaling complexes. Nat. Neurosci. 3, 661–669.PubMedGoogle Scholar
  56. Hyson, R. L., and Rubel, E. W. (1995) Activity-dependent regulation of a ribosomal RNA epitope in the chick cochlear nucleus. Brain Res. 672, 196–204.PubMedGoogle Scholar
  57. Irwin, S. A., Patel, B., Idupulapati, M., Harris, J. B., Crisostomo, R. A., Larsen, B. P., Kooy, F., Willems, P. J., Cras, P., Kozlowski, P. B., et al. (2001) Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination. Am. J. Med. Genet. 98, 161–167.PubMedGoogle Scholar
  58. Jones, R. B., Gordus, A., Krall, J. A., and MacBeath, G. (2006) A quantitative protein interaction network for the ErbB receptors using protein microarrays. Nature 439, 168–174.PubMedGoogle Scholar
  59. Jordan, B. A., Fernholz, B. D., Boussac, M., Xu, C., Grigorean, G., Ziff, E. B., and Neubert, T. A. (2004) Identification and verification of novel rodent postsynaptic density proteins. Mol. Cell Proteomics. 3, 857–871.PubMedGoogle Scholar
  60. Jordan, B. A., Fernholz, B. D., Neubert, T. A., and Ziff, E. B. (2006) The Dynamic Synapse: Molecular Methods in Ionotropic Receptor Biology. CRC/Taylor & Francis, Boc Raton.Google Scholar
  61. Jordan, B. A., Fernholz, B. D., Khatri, L., Ziff, E. B. (2007) Activity-dependent AIDA-1 nuclear signaling regulates nucleolar numbers and protein synthesis in neurons. Nat. Neurosci. 10, 427–35.PubMedGoogle Scholar
  62. Kaltschmidt, C., Kaltschmidt, B., and Baeuerle, P. A. (1995) Stimulation of ionotropic gluta mate receptors activates transcription factor NF-kappa B in primary neurons. Proc. Natl. Acad. Sci. USA 92, 9618–9622.PubMedGoogle Scholar
  63. Kameoka, S., Duque, P., and Konarska, M. M. (2004) p54(nrb) associates with the 5’ splice site within large transcription/splicing complexes. EMBO J. 23, 1782–1791.PubMedGoogle Scholar
  64. Kandel, E. R. (2001) The molecular biology of memory storage: a dialogue between genes and synapses. Science 294, 1030–1038.PubMedGoogle Scholar
  65. Kaul, S. C., Kawai, R., Nomura, H., Mitsui, Y., Reddel, R. R., and Wadhwa, R. (1999) Identi fication of a 55-kDa ezrin-related protein that induces cytoskeletal changes and localizes to the nucleolus. Exp. Cell Res. 250, 51–61.PubMedGoogle Scholar
  66. Kausalya, P. J., Phua, D. C., and Hunziker, W. (2004) Association of ARVCF with zonula occludens (ZO)-1 and ZO-2: binding to PDZ-domain proteins and cell-cell adhesion regulate plasma membrane and nuclear localization of ARVCF. Mol. Biol. Cell 15, 5503–5515.PubMedGoogle Scholar
  67. Kavanagh, E., Buchert, M., Tsapara, A., Choquet, A., Balda, M. S., Hollande, F., and Matter, K. (2006) Functional interaction between the ZO-1-interacting transcription factor ZONAB/DbpA and the RNA processing factor symplekin. J. Cell Sci. 119, 5098–5105.PubMedGoogle Scholar
  68. Kelleher, R. J., 3rd, Govindarajan, A., Jung, H. Y., Kang, H., and Tonegawa, S. (2004) Trans lational control by MAPK signaling in long-term synaptic plasticity and memory. Cell 116, 467–479.PubMedGoogle Scholar
  69. Kelly, K. F., Spring, C. M., Otchere, A. A., and Daniel, J. M. (2004) NLS-dependent nuclear localization of p120ctn is necessary to relieve Kaiso-mediated transcriptional repression. J. Cell Sci. 117, 2675–2686.PubMedGoogle Scholar
  70. Kennedy, M. B. (1993) The postsynaptic density. Curr Opin Neurobiol 3, 732–737.PubMedGoogle Scholar
  71. Kohu, K., Ogawa, F., and Akiyama, T. (2002) The SH3, HOOK and guanylate kinase-like domains of hDLG are important for its cytoplasmic localization. Genes Cells 7, 707–715.PubMedGoogle Scholar
  72. Kress, T. L., Yoon, Y. J., and Mowry, K. L. (2004) Nuclear RNP complex assembly initiates cytoplasmic RNA localization. J. Cell Biol. 165, 203–211.PubMedGoogle Scholar
  73. Lafarga, M., Andres, M. A., Fernandez-Viadero, C., Villegas, J., and Berciano, M. T. (1995) Number of nucleoli and coiled bodies and distribution of fibrillar centres in differentiating Purkinje neurons of chick and rat cerebellum. Anat. Embryol. (Berl) 191, 359–367.Google Scholar
  74. Laggerbauer, B., Ostareck, D., Keidel, E. M., Ostareck-Lederer, A., and Fischer, U. (2001) Evidence that fragile X mental retardation protein is a negative regulator of translation. Hum. Mol. Genet. 329–338.Google Scholar
  75. Lallena, M. J., Martinez, C., Valcarcel, J., and Correas, I. (1998) Functional association of nuclear protein 4.1 with pre-mRNA splicing factors. J. Cell Sci. 111 (Pt 14), 1963–1971.PubMedGoogle Scholar
  76. Lewis, B. P., Green, R. E., and Brenner, S. E. (2003) Evidence for the widespread coupling of alternative splicing and nonsense-mediated mRNA decay in humans. Proc. Natl. Acad. Sci. USA 100, 189–192.PubMedGoogle Scholar
  77. Li, K., Hornshaw, M. P., van Minnen, J., Smalla, K. H., Gundelfinger, E. D., and Smit, A. B. (2005) Organelle proteomics of rat synaptic proteins: correlation-profiling by isotope- coded affinity tagging in conjunction with liquid chromatography-tandem mass spectrometry to reveal post-synaptic density specific proteins. J. Proteome Res. 4, 725–733.PubMedGoogle Scholar
  78. Li, K. W., Hornshaw, M. P., Van Der Schors, R. C., Watson, R., Tate, S., Casetta, B., Jimenez, C. R., Gouwenberg, Y., Gundelfinger, E. D., Smalla, K. H., and Smit, A. B. (2004) Proteomics analysis of rat brain postsynaptic density. Implications of the diverse protein functional groups for the integration of synaptic physiology. J. Biol. Chem. 279, 987–1002.Google Scholar
  79. Li, Y., Yu, W. H., Ren, J., Chen, W., Huang, L., Kharbanda, S., Loda, M., and Kufe, D. (2003) Heregulin targets gamma-catenin to the nucleolus by a mechanism dependent on the DF3/MUC1 oncoprotein. Mol. Cancer Res. 1, 765–775.PubMedGoogle Scholar
  80. Li, Z., Zhang, Y., Ku, L., Wilkinson, K. D., Warren, S. T., and Feng, Y. (2001) The fragile X mental retardation protein inhibits translation via interacting with mRNA. Nucleic Acids Res. 29, 2276–2283.PubMedGoogle Scholar
  81. Lipscombe, D., Madison, D. V., Poenie, M., Reuter, H., Tsien, R. W., and Tsien, R. Y. (1988) Imaging of cytosolic Ca2+ transients arising from Ca2+ stores and Ca2+ channels in sympathetic neurons. Neuron 1, 355–365.PubMedGoogle Scholar
  82. Liu, Y. Z., Dawson, S. J., and Latchman, D. S. (1996) Alternative splicing of the Brn-3a and Brn-3b transcription factor RNAs is regulated in neuronal cells. J. Mol. Neurosci. 7, 77- 85.PubMedGoogle Scholar
  83. Macchi, P., Brownawell, A. M., Grunewald, B., DesGroseillers, L., Macara, I. G., and Kiebler, M. A. (2004) The brain-specific double-stranded RNA-binding protein Staufen2: nucleolar accumulation and isoform-specific exportin-5-dependent export. J. Biol. Chem. 279, 31440–31444.PubMedGoogle Scholar
  84. Marambaud, P., Wen, P. H., Dutt, A., Shioi, J., Takashima, A., Siman, R., and Robakis, N. K. (2003) A CBP binding transcriptional repressor produced by the PS1/epsilon-cleavage of N-cadherin is inhibited by PS1 FAD mutations. Cell 114, 635–645.PubMedGoogle Scholar
  85. Martel, C., Macchi, P., Furic, L., Kiebler, M. A., and Desgroseillers, L. (2006) Staufen1 is imported into the nucleolus via a bipartite nuclear localization signal and several modulatory determinants. Biochem. J. 393, 245–254.PubMedGoogle Scholar
  86. Matsuda, S., Mikawa, S., and Hirai, H. (1999) Phosphorylation of serine-880 in GluR2 by protein kinase C prevents its C terminus from binding with glutamate receptor-interacting protein. J. Neurochem. 73, 1765–1768.PubMedGoogle Scholar
  87. Mayeda, A., and Krainer, A. R. (1992) Regulation of alternative pre-mRNA splicing by hnRNP A1 and splicing factor SF2. Cell 68, 365–375.PubMedGoogle Scholar
  88. McGaugh, J. L. (2000) Memory–a century of consolidation. Science 287, 248–251.PubMedGoogle Scholar
  89. Meissner, M., Lopato, S., Gotzmann, J., Sauermann, G., and Barta, A. (2003) Proto- oncoprotein TLS/FUS is associated to the nuclear matrix and complexed with splicing factors PTB, SRm160, and SR proteins. Exp. Cell Res. 283, 184–195.PubMedGoogle Scholar
  90. Mu, Y., Otsuka, T., Horton, A. C., Scott, D. B., and Ehlers, M. D. (2003) Activity-dependent mRNA splicing controls ER export and synaptic delivery of NMDA receptors. Neuron 40, 581–594.PubMedGoogle Scholar
  91. Murase, S., Mosser, E., and Schuman, E. M. (2002) Depolarization drives beta-Catenin into neuronal spines promoting changes in synaptic structure and function. Neuron 35, 91–105.PubMedGoogle Scholar
  92. Nair, R., Carter, P., and Rost, B. (2003) NLSdb: database of nuclear localization signals. Nucleic Acids Res 31, 397–399.PubMedGoogle Scholar
  93. Nakata, A., Ito, T., Nagata, M., Hori, S., and Sekimizu, K. (2004) GRIP1tau, a novel PDZ domain-containing transcriptional activator, cooperates with the testis-specific transcription elongation factor SII-T1. Genes Cells 9, 1125–1135.PubMedGoogle Scholar
  94. Nimchinsky, E. A., Oberlander, A. M., and Svoboda, K. (2001) Abnormal development of dendritic spines in FMR1 knock-out mice. J. Neurosci. 21, 5139–5146.PubMedGoogle Scholar
  95. Osawa, M., Tong, K. I., Lilliehook, C., Wasco, W., Buxbaum, J. D., Cheng, H. Y., Penninger, J. M., Ikura, M., and Ames, J. B. (2001) Calcium-regulated DNA binding and oligomerization of the neuronal calcium-sensing protein, calsenilin/DREAM/KChIP3. J. Biol. Chem. 276, 41005–41013.PubMedGoogle Scholar
  96. Pastalkova, E., Serrano, P., Pinkhasova, D., Wallace, E., Fenton, A. A., and Sacktor, T. C. (2006) Storage of spatial information by the maintenance mechanism of LTP. Science 313, 1141–1144.PubMedGoogle Scholar
  97. Patton, J. G., Porro, E. B., Galceran, J., Tempst, P., and Nadal-Ginard, B. (1993) Cloning and characterization of PSF, a novel pre-mRNA splicing factor. Genes Dev. 7, 393–406.PubMedGoogle Scholar
  98. Peng, J., Kim, M. J., Cheng, D., Duong, D. M., Gygi, S. P., and Sheng, M. (2004) Semi-quantitative proteomic analysis of rat forebrain postsynaptic density fractions by mass spec trometry. J. Biol. Chem. 14, 21003–21011.Google Scholar
  99. Pfeiffer, B. E., and Huber, K. M. (2006) Current advances in local protein synthesis and synaptic plasticity. J. Neurosci. 26, 7147–7150.PubMedGoogle Scholar
  100. Phillips, G. R., Florens, L., Tanaka, H., Khaing, Z. Z., Fidler, L., Yates, J. R., 3rd, and Colman, D. R. (2005) Proteomic comparison of two fractions derived from the transsynaptic scaffold. J. Neurosci. Res 81, 762–775.PubMedGoogle Scholar
  101. Pinol-Roma, S., and Dreyfuss, G. (1992) Shuttling of pre-mRNA binding proteins between nucleus and cytoplasm. Nature 355, 730–732.PubMedGoogle Scholar
  102. Polesello, C., and Payre, F. (2004) Small is beautiful: what flies tell us about ERM protein function in development. Trends Cell Biol. 14, 294–302.PubMedGoogle Scholar
  103. Prieto, J. L., and McStay, B. (2005) Nucleolar biogenesis: the first small steps. Biochem. Soc. Trans. 33, 1441–1443.PubMedGoogle Scholar
  104. Rajan, P., Symes, A. J., and Fink, J. S. (1996) STAT proteins are activated by ciliary neurotrophic factor in cells of central nervous system origin. J. Neurosci. Res 43, 403–411.PubMedGoogle Scholar
  105. Ranum, L. P., and Cooper, T. A. (2006) RNA-mediated neuromuscular disorders. Annu. Rev. Neurosci. 29, 259–277.PubMedGoogle Scholar
  106. Reymann, K. G., and Frey, J. U. (2007) The late maintenance of hippocampal LTP: Requirements, phases, ’synaptic tagging’, ’late-associativity’ and implications. Neuropharmacol. 52, 24–40.Google Scholar
  107. Righi, M., Tongiorgi, E., and Cattaneo, A. (2000) Brain-derived neurotrophic factor (BDNF) induces dendritic targeting of BDNF and tyrosine kinase B mRNAs in hippocampal neurons through a phosphatidylinositol-3 kinase-dependent pathway. J. Neurosci. 20, 3165–3174.PubMedGoogle Scholar
  108. Roczniak-Ferguson, A., and Reynolds, A. B. (2003) Regulation of p120-catenin nucleocyto plasmic shuttling activity. J. Cell Sci. 116, 4201–4212.PubMedGoogle Scholar
  109. Rodova, M., Kelly, K. F., VanSaun, M., Daniel, J. M., and Werle, M. J. (2004) Regulation of the rapsyn promoter by kaiso and delta-catenin. Mol. Cell Biol. 24, 7188–7196.PubMedGoogle Scholar
  110. Rodriguez, M. A., Pesold, C., Liu, W. S., Kriho, V., Guidotti, A., Pappas, G. D., and Costa, E. (2000) Colocalization of integrin receptors and reelin in dendritic spine postsynaptic densities of adult nonhuman primate cortex. Proc. Natl. Acad. Sci. USA 97, 3550–3555.PubMedGoogle Scholar
  111. Rook, M. S., Lu, M., and Kosik, K. S. (2000) CaMKIIalpha 3’ untranslated region-directed mRNA translocation in living neurons: visualization by GFP linkage. J. Neurosci. 20, 6385–6393.PubMedGoogle Scholar
  112. Rothrock, C. R., House, A. E., and Lynch, K. W. (2005) HnRNP L represses exon splicing via a regulated exonic splicing silencer. EMBO J. 24, 2792–2802.PubMedGoogle Scholar
  113. Salomon, D., Sacco, P. A., Roy, S. G., Simcha, I., Johnson, K. R., Wheelock, M. J., and Ben-Ze’ev, A. (1997) Regulation of beta-catenin levels and localization by overexpression of plakoglobin and inhibition of the ubiquitin-proteasome system. J. Cell Biol. 139, 1325–1335.PubMedGoogle Scholar
  114. Santoni, V., Molloy, M., and Rabilloud, T. (2000) Membrane proteins and proteomics: unamour impossible? Electrophoresis 21, 1054–1070.PubMedGoogle Scholar
  115. Scheiffele, P., Fan, J., Choih, J., Fetter, R., and Serafini, T. (2000) Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons. Cell 101, 657–669.PubMedGoogle Scholar
  116. Schuman, E. M., Dynes, J. L., and Steward, O. (2006) Synaptic regulation of translation of dendritic mRNAs. J. Neurosci. 26, 7143–7146.PubMedGoogle Scholar
  117. Shen, L., Liang, F., Walensky, L. D., and Huganir, R. L. (2000) Regulation of AMPA receptor GluR1 subunit surface expression by a 4. 1N-linked actin cytoskeletal association. J. Neurosci. 20, 7932–7940.PubMedGoogle Scholar
  118. Shin, C., and Manley, J. L. (2004) Cell signalling and the control of pre-mRNA splicing. Nat Rev Mol Cell Biol 5, 727–738.PubMedGoogle Scholar
  119. Si, K., Giustetto, M., Etkin, A., Hsu, R., Janisiewicz, A. M., Miniaci, M. C., Kim, J. H., Zhu, H., and Kandel, E. R. (2003) A neuronal isoform of CPEB regulates local protein synthesis and stabilizes synapse-specific long-term facilitation in aplysia. Cell 115, 893–904.PubMedGoogle Scholar
  120. Siman, R., and Noszek, J. C. (1988) Excitatory amino acids activate calpain I and induce structural protein breakdown in vivo. Neuron 1, 279–287.PubMedGoogle Scholar
  121. Simcha, I., Geiger, B., Yehuda-Levenberg, S., Salomon, D., and Ben-Ze’ev, A. (1996) Suppression of tumorigenicity by plakoglobin: an augmenting effect of N-cadherin. J. Cell Biol. 133, 199–209.PubMedGoogle Scholar
  122. Solovei, I., Grandi, N., Knoth, R., Volk, B., and Cremer, T. (2004) Positional changes of pericentromeric heterochromatin and nucleoli in postmitotic Purkinje cells during murine cerebellum development. Cytogenetic and Genome Research 105, 302–310.Google Scholar
  123. Sossin, W. S., and DesGroseillers, L. (2006) Intracellular trafficking of RNA in neurons. Traffic 7, 1581–1589.PubMedGoogle Scholar
  124. Steward, O., and Falk, P. M. (1986) Protein-synthetic machinery at postsynaptic sites during synaptogenesis: a quantitative study of the association between polyribosomes and developing synapses. J. Neurosci. 6, 412–423.PubMedGoogle Scholar
  125. Steward, O., and Levy, W. B. (1982) Preferential localization of polyribosomes under the base of dendritic spines in granule cells of the dentate gyrus. J. Neurosci. 2, 284–291.PubMedGoogle Scholar
  126. Steward, O., and Worley, P. F. (2001a) A cellular mechanism for targeting newly synthesized mRNAs to synaptic sites on dendrites. Proc. Natl. Acad. Sci. USA 98, 7062–7068.Google Scholar
  127. Steward, O., and Worley, P. F. (2001b) Selective targeting of newly synthesized Arc mRNA to active synapses requires NMDA receptor activation. Neuron 30, 227–240.Google Scholar
  128. Tang, S. J., Meulemans, D., Vazquez, L., Colaco, N., and Schuman, E. (2001) A role for a rat homolog of staufen in the transport of RNA to neuronal dendrites. Neuron 32, 463–475.PubMedGoogle Scholar
  129. Thomas, K. L., Laroche, S., Errington, M. L., Bliss, T. V., and Hunt, S. P. (1994) Spatial and temporal changes in signal transduction pathways during LTP. Neuron 13, 737–745.PubMedGoogle Scholar
  130. Thompson, K. R., Otis, K. O., Chen, D. Y., Zhao, Y., O’Dell, T. J., and Martin, K. C. (2004) Synapse to nucleus signaling during long-term synaptic plasticity; a role for the classical active nuclear import pathway. Neuron 44, 997–1009.PubMedGoogle Scholar
  131. Tongiorgi, E., Righi, M., and Cattaneo, A. (1997) Activity-dependent dendritic targeting of BDNF and TrkB mRNAs in hippocampal neurons. J. Neurosci. 17, 9492–9505.PubMedGoogle Scholar
  132. Ule, J., Ule, A., Spencer, J., Williams, A., Hu, J. S., Cline, M., Wang, H., Clark, T., Fraser, C., Ruggiu, M., et al. (2005) Nova regulates brain-specific splicing to shape the synapse. Nat. Genet. 37, 844–852.PubMedGoogle Scholar
  133. Usacheva, A., Smith, R., Minshall, R., Baida, G., Seng, S., Croze, E., and Colamonici, O. (2001) The WD motif-containing protein receptor for activated protein kinase C (RACK1) is required for recruitment and activation of signal transducer and activator of transcription 1 through the type I interferon receptor. J. Biol. Chem. 276, 22948–22953.PubMedGoogle Scholar
  134. Vinade, L., Chang, M., Schlief, M. L., Petersen, J. D., Reese, T. S., Tao-Cheng, J. H., and Dosemeci, A. (2003) Affinity purification of PSD-95-containing postsynaptic complexes. J. Neurochem. 87, 1255–1261.PubMedGoogle Scholar
  135. Walikonis, R. S., Jensen, O. N., Mann, M., Provance, D. W., Jr, Mercer, J. A., and Kennedy, M. B. (2000) Identification of Proteins in the Postsynaptic Density Fraction by Mass Spectrometry. J. Neurosci. 20, 4069–4080.PubMedGoogle Scholar
  136. Walsh, M. J., and Kuruc, N. (1992) The postsynaptic density: constituent and associated prot eins characterized by electrophoresis, immunoblotting, and peptide sequencing. J. Neuro chem. 59, 667–678.Google Scholar
  137. Wang, G. S., Hong, C. J., Yen, T. Y., Huang, H. Y., Ou, Y., Huang, T. N., Jung, W. G., Kuo, T. Y., Sheng, M., Wang, T. F., and Hsueh, Y. P. (2004) Transcriptional modification by a CASK-interacting nucleosome assembly protein. Neuron 42, 113–128.PubMedGoogle Scholar
  138. West, A. E., Griffith, E. C., and Greenberg, M. E. (2002) Regulation of transcription factors by neuronal activity. Nat. Rev. Neurosci. 3, 921–931.PubMedGoogle Scholar
  139. Williams, C. C., Allison, J. G., Vidal, G. A., Burow, M. E., Beckman, B. S., Marrero, L., and Jones, F. E. (2004) The ERBB4/HER4 receptor tyrosine kinase regulates gene expression by functioning as a STAT5A nuclear chaperone. J. Cell Biol. 167, 469–478.PubMedGoogle Scholar
  140. Woods, A. J., Roberts, M. S., Choudhary, J., Barry, S. T., Mazaki, Y., Sabe, H., Morley, S. J., Critchley, D. R., and Norman, J. C. (2002) Paxillin associates with poly(A)-binding protein 1 at the dense endoplasmic reticulum and the leading edge of migrating cells. J. Biol. Chem. 277, 6428–6437.PubMedGoogle Scholar
  141. Wu, L., Wells, D., Tay, J., Mendis, D., Abbott, M. A., Barnitt, A., Quinlan, E., Heynen, A., Fallon, J. R., and Richter, J. D. (1998) CPEB-mediated cytoplasmic polyadenylation and the regulation of experience-dependent translation of alpha-CaMKII mRNA at synapses. Neuron 21, 1129–1139.PubMedGoogle Scholar
  142. Wyszynski, M., Lin, J., Rao, A., Nigh, E., Beggs, A. H., Craig, A. M., and Sheng, M. (1997) Competitive binding of alpha-actinin and calmodulin to the NMDA receptor. Nature 385, 439–442.PubMedGoogle Scholar
  143. Xie, J., Jan, C., Stoilov, P., Park, J., and Black, D. L. (2005) A consensus CaMK IV-responsive RNA sequence mediates regulation of alternative exons in neurons. RNA 11, 1825–1834.PubMedGoogle Scholar
  144. Xu, H., and Hebert, M. D. (2005) A novel EB-1/AIDA-1 isoform, AIDA-1c, interacts with the Cajal body protein coilin. BMC. Cell Biol. 6, 23.PubMedGoogle Scholar
  145. Yoshimura, Y., Yamauchi, Y., Shinkawa, T., Taoka, M., Donai, H., Takahashi, N., Isobe, T., and Yamauchi, T. (2004) Molecular constituents of the postsynaptic density fraction revealed by proteomic analysis using multidimensional liquid chromatography-tandem mass spectrometry. J. Neurochem. 88, 759–768.PubMedGoogle Scholar
  146. Yu, G., Zerucha, T., Ekker, M., and Rubenstein, J. L. (2001) Evidence that GRIP, a PDZ-domain protein which is expressed in the embryonic forebrain, co-activates transcription with DLX homeodomain proteins. Brain Res. Dev. Brain Res. 130, 217–230.PubMedGoogle Scholar
  147. Zatsepina, O., Baly, C., Chebrout, M., and Debey, P. (2003) The step-wise assembly of a functional nucleolus in preimplantation mouse embryos involves the cajal (coiled) body. Dev. Biol. 253, 66–83.PubMedGoogle Scholar
  148. Ziff, E. B. (1997) Enlightening the postsynaptic density. Neuron 19, 1163–1174.PubMedGoogle Scholar
  149. Zinszner, H., Sok, J., Immanuel, D., Yin, Y., and Ron, D. (1997) TLS (FUS) binds RNA in vivo and engages in nucleo-cytoplasmic shuttling. J. Cell Sci. 110, 1741–1750.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Bryen A. Jordan
  • Edward B. Ziff

There are no affiliations available

Personalised recommendations