Molecular Neurobiology

, Volume 32, Issue 2, pp 113–121 | Cite as

Neuronal homeostasis through translational control

Article

Abstract

Translational repression is a key component of the mechanism that establishes segment polarity during early embryonic development in the fruitfly Drosophila melanogaster. Two proteins, Pumilio (Pum) and Nanos, block the translation of hunchback messenger RNA in only the posterior segments, thereby promoting an abdominal fate. More recent studies focusing on postembryonic neuronal function have shown that Pum is also integral to numerous mechanisms that allow neurons to adapt to the changing requirements placed on them in a dynamic nervous system. These mechanisms include those contributing to dendritic structure, synaptic growth, neuronal excitability, and formation of long-term memory. This article describes these new studies and highlights the role of translational repression in regulation of neuronal processes that compensate for change.

Index Entries

Excitability glutamate neural activity neuromuscular junction Nanos paralytic pumilio translational repression 

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References

  1. 1.
    Turrigiano G. G. and Nelson S. B. (2000) Hebb and homeostasis in neuronal plasticity. Curr. Opin. Neurobiol. 10, 358–364.PubMedCrossRefGoogle Scholar
  2. 2.
    Ye B., Petritsch C., Clark I. E., Gavis E. R., Jan L. Y., and Jan Y. H. (2004) nanos and pumilio are essential for dendrite morphogenesis in Drosophila peripheral neurons. Curr. Biol. 14, 314–321.PubMedCrossRefGoogle Scholar
  3. 3.
    Menon K. P., Sanyal S., Habara, Y., et al. (2004) The translational repressor Pumilio regulates presynaptic morphology and controls postsynaptic accumulation of translation factor eIF-4E. Neuron. 44, 663–676.PubMedCrossRefGoogle Scholar
  4. 4.
    Mee C. J., Pym E. C. G., Moffat K. G., and Baines R. A. (2004) Regulation of neuronal excitability through pumilio-dependent control of a sodium channel gene. J. Neurosci. 24, 8695–8703.PubMedCrossRefGoogle Scholar
  5. 5.
    Dubnau J., Chian A. S., Grady L., et al. (2003) The staufen/pumilio pathway is involved in Drosophila long-term memory. Curr. Biol. 13, 286–296.PubMedCrossRefGoogle Scholar
  6. 6.
    Tautz D. (1988). Regulation of Drosophila segmentation gene hunchback by two maternal morphogenetic centres. Nature 332, 281–284.PubMedCrossRefGoogle Scholar
  7. 7.
    Wharton R. P. and Struhl G. (1991) RNA regulatory elements mediate control of Drosophila body pattern by the posterior morphogen nanos. Cell 67, 955–967.PubMedCrossRefGoogle Scholar
  8. 8.
    Wharton R. P., Sonoda J., Lee T., Patterson M., and Murata Y. (1998) The Pumilio RNA-binding domain is also a translational repressor. Mol. Cell 1, 863–872.PubMedCrossRefGoogle Scholar
  9. 9.
    Zamore P. D., Williamson J. R., and Lehmann R. (1997) The Pumilio protein binds RNA through a conserved domain that defines a new class of RNA-binding proteins. RNA 3, 1421–1433.PubMedGoogle Scholar
  10. 10.
    Wreden C., Verotti A. C., Schisa J. A., Lieberfarb M. E., and Strickland S. (1997) Nanos and pumilio establish embryonic polarity in Drosophila by promoting posterior deadenylation of hunchback mRNA. Development 124, 3015–3023.PubMedGoogle Scholar
  11. 11.
    Sonoda J. and Wharton R. P. (1999) Recruitment of Nanos to hunchback mRNA by Pumilio. Genes Dev. 13, 2704–2712.PubMedCrossRefGoogle Scholar
  12. 12.
    Sonoda J. and Wharton R. P. (2001) Drosophila Brain Tumor is a translational repressor. Genes Dev. 15, 762–773.PubMedCrossRefGoogle Scholar
  13. 13.
    Chagnovich D. and Lehmann R. (2001) Poly(A)-independent regulation of maternal hunchback translation in the Drosophila embryo. Proc. Natl. Acad. Sci. USA 98, 11,359–11,364.CrossRefGoogle Scholar
  14. 14.
    Dean K. A., Aggarwal A. K., and Wharton R. P. (2002) Translational repressors in Drosophila. Trends Neurosci. 18, 572–576.Google Scholar
  15. 15.
    Gavis E. R. (2001). Over the rainbow to translational control. Nat. Struct. Biol. 18, 387–389.CrossRefGoogle Scholar
  16. 16.
    Parisi M. and Lin H. (2000) Translational repression: A duet of nanos and pumilio. Curr. Biol. 10, R81-R83.PubMedCrossRefGoogle Scholar
  17. 17.
    Jan Y. H. and Jan L. Y. (2003) The control of dendrite development. Neuron 40, 229–242.PubMedCrossRefGoogle Scholar
  18. 18.
    Wässle H. and Boycott B. B. (1991) Functional architecture of the mammalian retina. Physiol. Rev. 71, 447–478.PubMedGoogle Scholar
  19. 19.
    MacNeil M. A. and Masland R. H. (1998) Extreme diversity among amacrine cells: implications for function. Neuron 20, 971–982.PubMedCrossRefGoogle Scholar
  20. 20.
    Sestan N., Artavanis-Tsakonas S., and Rakic P. (1999) Contact-dependent inhibition of cortical neurite growth mediated by notch signalling. Science 286, 741–746.PubMedCrossRefGoogle Scholar
  21. 21.
    Logan M. A. and Vetter M. L. (2004) Do-it-yourself tiling: dendritic growth in the absence of homotypic contacts. Neuron 43, 439–446.PubMedCrossRefGoogle Scholar
  22. 22.
    Steward O. and Schuman E. M. (2001) Protein synthesis at synaptic sites on dendrites. Annu. Rev. Neurosci. 24, 229–325.CrossRefGoogle Scholar
  23. 23.
    Tang A. J. and Schuman E. M. (2000) Protein synthesis in the dendrite. Phil. Trans. R. Soc. Lond. B. 357, 521–529.CrossRefGoogle Scholar
  24. 24.
    Grueber W. B., Ye B., Moore A. W., Jan L. Y., and Jan Y. N. (2003) Dendrites of distinct classes of Drosophila sensory neurons show different capacities for homotypic repulsion. Curr. Biol. 13, 618–626.PubMedCrossRefGoogle Scholar
  25. 25.
    Knowles R. B., Sabry J. H., Martone M. E., et al. (1996) Translocation of RNA granules in living neurons. J. Neurosci. 16, 7812–7820.PubMedGoogle Scholar
  26. 26.
    Davis G. W. and Bezprozvanny I. (2001) Maintaining the stability of neural function: a homeostatic hypothesis. Annu. Rev. Physiol. 63, 847–869.PubMedCrossRefGoogle Scholar
  27. 27.
    Davis G. W. and Goodman C. S. (1998) Synapse-specific control of synaptic efficacy at the terminals of a single neuron. Nature 392, 82–86.PubMedCrossRefGoogle Scholar
  28. 28.
    Sigrist S. J., Thiel P. R., Reiff D. F., Lachance P. E., Lasko P., and Schuster C. M. (2000) Postsynaptic translation affects the efficacy and morphology of neuromuscular junctions. Nature 405, 1062–1065.PubMedCrossRefGoogle Scholar
  29. 29.
    Sigrist S. J., Thiel P. R., Reiff D. F., and Schuster C. M. (2002) The postsynaptic glutamate receptor subunit DgluR-IIA mediates long-term plasticity in Drosophila. J. Neurosci. 22, 7362–7372.PubMedGoogle Scholar
  30. 30.
    Edwards T. A., Pyle S. E., Wharton R. P., and Aggarwal A. K. (2001) Structure of Pumilio reveals similarity between RNA and peptide binding motifs. Cell 105, 281–289.PubMedCrossRefGoogle Scholar
  31. 31.
    Wang X., Zamore P. D., and Hall T. M. (2001) Crystal structure of a Pumilio homology domain. Mol. Cell 7, 855–865.PubMedCrossRefGoogle Scholar
  32. 32.
    Desai N. S., Rutherford L. C., and Turrigiano G. G. (1999) Plasticity in the intrinsic excitability of cortical pyramidal neurons. Nat. Neurosci. 2, 515–520.PubMedCrossRefGoogle Scholar
  33. 33.
    Baines R. A., Uhler J. P., Thompson A., Sweeney S. T., and Bate M. (2001) Altered electrical properties in Drosophila neurons developing without synaptic transmission. J. Neurosci. 21, 1523–1531.PubMedGoogle Scholar
  34. 34.
    Baines R. A. (2003) Postsynaptic protein kinase A reduces neuronal excitability in response to increased synaptic excitation in the Drosophila CNS. J. Neurosci. 23, 8664–8672.PubMedGoogle Scholar
  35. 35.
    Li M., West J. W., Lai Y., Scheuer T., and Catterall W. A. (1992) Functional modulation of brain sodium channels by cAMP-dependent phosphorylation. Neuron 8, 1151–1159.PubMedCrossRefGoogle Scholar
  36. 36.
    Smith R. D. and Goldin A. L. (1997) Phosphorylation at a single site in the rat brain sodium channel is necessary and sufficient for current reduction by protein kinase A. J. Neurosci. 17, 6086–6093.PubMedGoogle Scholar
  37. 37.
    Catterall W. A. (2000) From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron 26, 13–25.PubMedCrossRefGoogle Scholar
  38. 38.
    Stern M., Blake N., Zondlo N., and Walters K. (1995) Increased neuronal excitability conferred by a mutation in the Drosophila bemused gene. J. Neurogenet. 10, 103–118.PubMedGoogle Scholar
  39. 39.
    Stern M. and Ganetzky B. (1989) Altered synaptic transmission in Drosophila hyperkinetic mutants. J. Neurogenet. 5, 215–228.PubMedGoogle Scholar
  40. 40.
    Stern M., Kreber R., and Ganetzky B. (1990) Dosage effects of a Drosophila sodium channel gene on behavior and axonal excitability. Genetics 124, 133–143.PubMedGoogle Scholar
  41. 41.
    Schweers B. A., Walters K. J., and Stern M. (2002) The Drosophila melanogaster translational repressor pumilio regulates neuronal excitability. Genetics 161, 1177–1185.PubMedGoogle Scholar
  42. 42.
    Barker D. D., Wang C., Moore J., Dickinson L. K., and Lehmann R. (1992) Pumilio is essential for function but not for distribution of the Drosophila abdominal determinant Nanos. Genes Dev. 6, 2312–2326.PubMedCrossRefGoogle Scholar
  43. 43.
    Macdonald P. M. (1992) The Drosophila pumilio gene: an unusually long transcription unit and an unusual protein. Development 114, 221–232.PubMedGoogle Scholar
  44. 44.
    Zhang B., Gallegos M., Puoti A., et al. (1997) A conserved RNA-binding protein that regulates sexual fates in the C. elegans hermaphrodite germ line. Nature 390, 477–484.PubMedCrossRefGoogle Scholar
  45. 45.
    Spassov D. S. and Jurecic R. (2002) Cloning and comparative sequence analysis of PUM1 and PUM2 genes, human members of the Pumilio family of RNA-binding proteins. Gene 299, 195–204.PubMedCrossRefGoogle Scholar
  46. 46.
    Spassov D. S. and Jurecic R. (2003) MousePum1 and Pum2 genes, members of the Pumilio family of proteins, show differential expression in fetal and adult hematopoietic stem cells and progenitors. Blood Cells Mol. Dis. 30, 55–69.PubMedCrossRefGoogle Scholar
  47. 47.
    White E. K., Moore-Jarrett T., and Ruley H. E. (2001) PUM2, a novel murine puf protein, and its consensus RNA-binding site. RNA 12, 1855–1866.Google Scholar
  48. 48.
    Jaruzelska J., Kotecki M., Kusz K., Spik A., Firpo M., and Reijo Pera R. A. (2003) Conservation of a Pumilio-Nanos complex from Drosophila germ plasm to human germ cells. Dev. Genes Evol. 213, 120–126.PubMedGoogle Scholar
  49. 49.
    Haraguchi S., Tsuda M., Kitajima S., et al. (2003) nanos1: a mouse nanos gene expressed in the central nervous system is dispensable for normal development. Mech. Dev. 120, 721–731.PubMedCrossRefGoogle Scholar
  50. 50.
    Tsuda M., Sasaoka Y., Kiso M., et al. (2003) Conserved role of nanos proteins in germ cell development. Science 301, 1239–1241.PubMedCrossRefGoogle Scholar
  51. 51.
    Lipshitz H. D. and Smibert C. A. (2000) Mechanisms of RNA localization and translational regulation. Curr. Opin. Gen. Dev. 10, 476–488.CrossRefGoogle Scholar
  52. 52.
    Steward O. and Schuman E. M. (2003) Compartmentalized synthesis and degradation of protein in neurons. Neuron 40, 347–359.PubMedCrossRefGoogle Scholar
  53. 53.
    Miller S., Yasuda M., Coats J. K., Jones Y., Martone M. E., and Mayford M. (2002) Disruption of dendritic translation of CaMKIIalpha impairs stabilization of synaptic plasticity and memory consolidation. Neuron 36, 507–519.PubMedCrossRefGoogle Scholar
  54. 54.
    Kiebler M. A. and DesGroseillers L. (2000) Molecular insights into mRNA transport and local translation in the mammalian nervous system. Neuron 25, 19–28.PubMedCrossRefGoogle Scholar

Copyright information

© The Humana Press Inc 2005

Authors and Affiliations

  1. 1.Neuroscience Group, Department of Biological SciencesUniversity of WarwickCoventryUnited Kingdom

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