Skip to main content

Advertisement

SpringerLink
Log in

3′UTR-Dependent Localization of a Purkinje Cell Messenger RNA in Dendrites

  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

Pcp2(L7) is a Purkinje cell-specific GoLoco domain protein that modulates activation of Gαi/o proteins by G protein-coupled receptors. A likely downstream effector of this pathway is the P-type Ca2+ channel, and thereby, the intrinsic electrophysiology of Purkinje cells could be modulated by Pcp2(L7). It has long been known that the Pcp2(L7) mRNA is abundantly localized in dendrites, suggesting the possibility of distal synthesis and local changes in levels of the protein. As a first step to uncover the trafficking and translational mechanisms for this mRNA, we have begun identifying the cis-acting sequences important for its localization in dendrites. Using expression of modified transgenes in vivo, we show that the 3′UTR, only 65 bases long, is necessary in this process.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Notes

  1. These results were reported in part at a meeting: Serinagaoglu, Y., Iscru, E.M., Tian, J., Bishop, G.A., Morgan, J.I., Zhu, M.X., Oberdick, J. Sensorimotor behavioral changes and alteration of Purkinje cell firing patterns in Pcp2(L7) null mutant mice. Program No. 986.2. 2005 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2005. Online.

References

  1. Kang H, Schuman EM (1996) A requirement for local protein synthesis in neurotrophin-induced hippocampal synaptic plasticity. Science 273:1402–1406

    Article  PubMed  CAS  Google Scholar 

  2. Steward O, Wallace C, Lyford G, Worley P (1998) Synaptic activation causes the mRNA for the IEG Arc to localize selectively near activated postsynaptic sites on dendrites. Neuron 21:741–751

    Article  PubMed  CAS  Google Scholar 

  3. Scheetz AJ, Nairn AC, Constantine-Paton M (2000) NMDA receptor-mediated control of protein synthesis at developing synapses. Nat Neurosci 3:211–217

    Article  PubMed  CAS  Google Scholar 

  4. Tiruchinapalli DM, Oleynikov Y, Kelic S, Shenoy SM, Hartley A, Stanton PK, Singer RH, Bassell GJ (2003) Activity-dependent trafficking and dynamic localization of zipcode binding protein 1 and beta-actin mRNA in dendrites and spines of hippocampal neurons. J Neurosci 23:3251–3261

    PubMed  CAS  Google Scholar 

  5. Steward O, Schuman EM (2001) Protein synthesis at synaptic sites on dendrites. Annu Rev Neurosci 24:299–325

    Article  PubMed  CAS  Google Scholar 

  6. Wells DG, Richter JD, Fallon JR (2000) Molecular mechanisms for activity-regulated protein synthesis in the synapto-dendritic compartment. Curr Opin Neurobiol 10:132–137

    Article  PubMed  CAS  Google Scholar 

  7. Bian F, Chu T, Schilling K, Oberdick J (1996) Differential mRNA transport and the regulation of protein synthesis: selective sensitivity of Purkinje cell dendritic mRNAs to translational inhibition. Mol Cell Neurosci 7:116–133

    Article  PubMed  CAS  Google Scholar 

  8. Siderovski DP, Diversé-Pierlussi MA, De Vries L (1999) The GoLoco motif: a Galphai/o binding motif and potential guanine-nucleotide exchange factor. Trends Biochem Sci 24:340–341

    Article  PubMed  CAS  Google Scholar 

  9. Zhang X, Zhang H, Oberdick J (2002) Conservation of the developmentally regulated dendritic localization of a Purkinje cell-specific mRNA that encodes a G-protein modulator: comparison of rodent and human Pcp2(L7) gene structure and expression. Mol Brain Res 105:1–10

    Article  PubMed  Google Scholar 

  10. Willard FS, McCudden CR, Siderovski DP (2006) G-protein alpha subunit interaction and guanine nucleotide dissociation inhibitor activity of the dual GoLoco motif protein PCP-2 (Purkinje cell protein-2). Cell Signal 18:1226–1234

    Article  PubMed  CAS  Google Scholar 

  11. Oberdick J, Levinthal F, Levinthal C (1988) A Purkinje cell differentiation marker shows partial DNA sequence homology to the cellular sis/PDGF2 gene. Neuron 1:367–376

    Article  PubMed  CAS  Google Scholar 

  12. Oberdick J, Smeyne RJ, Mann JR, Zackson S, Morgan JI (1990) A promoter that drives transgene expression in cerebellar Purkinje and retinal bipolar neurons. Science 248:223–226

    Article  PubMed  CAS  Google Scholar 

  13. Berrebi AS, Oberdick J, Sangameswaran L, Christakos S, Morgan JI, Mugnaini E (1991) Cerebellar Purkinje cell markers are expressed in retinal bipolar neurons. J Comp Neurol 308:630–649

    Article  PubMed  CAS  Google Scholar 

  14. Vassileva G, Smeyne R, Morgan J (1997) Absence of neuroanatomical and behavioral deficits in L7/Pcp2 null mice. Mol Brain Res 46:333–337

    Article  PubMed  CAS  Google Scholar 

  15. Mohn AR, Feddersen RM, Nguyen MS, Koller BH (1997) Phenotypic analysis of mice lacking the highly abundant Purkinje cell and bipolar neuron-specific PCP2 protein. Mol Cell Neurosci 9:63–76

    Article  PubMed  CAS  Google Scholar 

  16. Kinoshita-Kawada M, Oberdick J, Zhu MX (2004) A Purkinje cell-specific GoLoco domain protein, L7/Pcp2, modulates receptor-mediated inhibition of Cav2.1 Ca2+ channels in a dose-dependent manner. Mol Brain Res 132:73–86

    Article  PubMed  CAS  Google Scholar 

  17. Kim JJ, Thompson RF (1997) Cerebellar circuits and synaptic mechanisms involved in classical eyeblink conditioning. Trends Neurosci 20:177–181

    Article  PubMed  CAS  Google Scholar 

  18. De Zeeuw CI, Hansel C, Bian F, Koekkoek SKE, van Alphen AM, Linden DJ, Oberdick J (1998) Expression of a protein kinase C inhibitor in Purkinje cells blocks cerebellar LTD and adaptation of the vestibulo-ocular reflex. Neuron 20:495–508

    Article  PubMed  Google Scholar 

  19. Raymond JL, Lisberger SG (2000) Hypotheses about the neural trigger for plasticity in the circuit for the vestibulo-ocular reflex. Prog Brain Res 124:235–246

    Article  PubMed  CAS  Google Scholar 

  20. Hansel C, Linden DJ, D’Angelo ED (2001) Beyond parallel fiber LTD: the diversity of synaptic and non-synaptic plasticity in the cerebellum. Nat Neurosci 4(5):467–475

    PubMed  CAS  Google Scholar 

  21. Blazquez PM, Hirata Y, Highstein SM (2004) The vestibulo-ocular reflex as a model system for motor learning: what is the role of the cerebellum? Cerebellum 3:188–192

    Article  PubMed  Google Scholar 

  22. Metzger F, Kapfhammer JP (2003) Protein kinase C: its role in activity-dependent Purkinje cell development and plasticity. Cerebellum 2:206–214

    Article  PubMed  CAS  Google Scholar 

  23. Smeyne RJ, Chu T, Lewin A, Bian F, S-Crisman S, Kunsch C, Lira S, Oberdick J (1995) Local control of granule cell generation by cerebellar Purkinje cells. Mol Cell Neurosci 6:230–251

    Article  PubMed  CAS  Google Scholar 

  24. Zhang X, Baader S, Bian F, Muller W, Oberdick J (2001) High level Purkinje cell-specific expression of green fluorescent protein in transgenic mice. Histochem Cell Biol 115:455–464

    PubMed  CAS  Google Scholar 

  25. Baader SL, Sanlioglu S, Berrebi AS, Parker-Thornburg J, Oberdick J (1998) Ectopic overexpression of Engrailed-2 in cerebellar Purkinje cells causes restricted cell loss and retarded external germinal layer development at lobule junctions. J Neurosci 18:1763–1773

    PubMed  CAS  Google Scholar 

  26. Wanner I, Baader S, Brich M, Oberdick J, Schilling K (1997) Subcellular localization of specific mRNAs and their protein products in Purkinje cells by combined fluorescence in situ hybrdization and immunocytochemistry. Histochem Cell Biol 108:345–357

    Article  PubMed  CAS  Google Scholar 

  27. Wanner I, Baader S, Oberdick J, Schilling K (2000) Changing subcellular distribution and activity-dependent utilization of a dendritically localized mRNA in developing Purkinje cells. Mol Cell Neurosci 15:275–287

    Article  PubMed  CAS  Google Scholar 

  28. Blichenberg A, Schwanke B, Rehbein M, Garner CC, Richter D, Kindler S (1999) Identification of a cis-acting dendritic targeting element in MAP2 mRNAs. J Neurosci 19:8818–8829

    PubMed  CAS  Google Scholar 

  29. Mori Y, Imaizumi K, Katayama T, Yoneda T, Tohyama M (2000) Two cis-acting elements in the 3′ untranslated region of a-CaMKII regulate its dendritic targeting. Nat Neurosci 3:1079–1084

    Article  PubMed  CAS  Google Scholar 

  30. Blichenberg A, Rehbein M, Muller R, Garner CC, Richter D, Kindler S (2001) Identification of a cis-acting dendritic targeting element in the mRNA encoding the a subunit of Ca2+/calmodulin-dependent protein kinase II. Eur J Neurosci 13:1881–1888

    Article  PubMed  CAS  Google Scholar 

  31. MacDonald PM, Struhl G (1988) Cis-acting sequences responsible for anterior localization of bicoid mRNA in Drosophila embryos. Nature 336:595–598

    Article  PubMed  CAS  Google Scholar 

  32. Gavis ER, Lehmann R (1994) Translational regulation of nanos by RNA localization. Nature 369:315–318

    Article  PubMed  CAS  Google Scholar 

  33. Ferrandon D, Elphick L, Nusslein-Volhard C, St Johnston D (1994) Staufen protein associates with the 3′YTP of bicoid mRNA to form particles that move in a microtubule-dependent manner. Cell 79:1221–1232

    Article  PubMed  CAS  Google Scholar 

  34. Palacios IM, St Johnston D (2001) Getting the message across: the intracellular localization of mRNAs in higher eukaryotes. Annu Rev Cell Dev Biol 17:569–614

    Article  PubMed  CAS  Google Scholar 

  35. Bockers TM, Segger-Junius M, Iglauer P, Bockmann J, Gundelfinger ED, Kreutz MR, Richter D, Kindler S, Kreienkamp H (2004) Differential expression and dendritic transcript localization of Shank family members: identification of a dendritic targeting element in the 3′ untranslated region of Shank1 mRNA. Mol Cell Neurosci 26:182–190

    Article  PubMed  Google Scholar 

  36. Serinagaoglu Y, Zhang R, Zhang Y, Zhang L, Hartt G, Young AP, Oberdick J (2007) A promoter element with enhancer properties, and the orphan nuclear receptor RORalpha, are required for Purkinje cell-specific expression of a Gi/o modulator. Mol Cell Neurosci 34:324–342

    Article  PubMed  CAS  Google Scholar 

  37. Simons MJ, Pellionisz A (2006) Genomics, morphogenesis, and biophysics: triangulation of Purkinje cell development. Cerebellum 5:27–35

    Article  PubMed  CAS  Google Scholar 

  38. Zuker M (2003) Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 31:3406–3415

    Article  PubMed  CAS  Google Scholar 

  39. Webb CKm McCudden CR, Willard FS, Kimple RJ, Siderovski DP, Oxford GS (2005) D2 dopamine receptor activation of potassium channels is selectively decoupled by Ga1-dpecific GoLoco motif peptides. J Neurochem 92:1408–1418

    Article  Google Scholar 

  40. Miller S, Yasuda M, Coats JK, Jones Y, Martone ME, Mayford M (2002) Disruption of dendritic translation of CaMKIIa impairs stabilization of synaptic plasticity and memory consolidation. Neuron 36:507–519

    Article  PubMed  CAS  Google Scholar 

  41. Huang YS, Carson JH, Barbarese E, Richter JD (2003) Facilitation of dendritic mRNA transport by CPEB. Genes Dev 17:638–653

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by NIH grant RO1-NS37504 and NSF grant IBN-0138147. Additional support was provided by NIH grant P30-NS045758.

Author information

Authors and Affiliations

  1. Center for Molecular Neurobiology and the Department of Neuroscience, The Ohio State University, 206 Rightmire Hall, 1060 Carmack Road, Columbus, OH, 43210, USA

    Rui Zhang, Xulun Zhang, Feng Bian, Xin-an Pu & John Oberdick

  2. Ohio State Biochemistry Program, The Ohio State University, Columbus, OH, USA

    Rui Zhang, Xulun Zhang & Feng Bian

  3. Anatomisches Institut, Rheinische Friedrich-Wilhelms Universität, Bonn, Germany

    Karl Schilling

Authors
  1. Rui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xulun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Feng Bian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xin-an Pu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Karl Schilling
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. John Oberdick
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John Oberdick.

Additional information

Rui Zhang and Xulun Zhang contributed equally to this work.

Electronic supplementary material

Below is the image is a link to a high resolution version

Figure S1

Background level of grains. In situ hybridization using 35S-labeled SV40 sense probe was performed on a sagittal section of P12 cerebellum from an L7-SV40 transgenic mouse. Arrows indicate the position of a Purkinje cell soma, which are typically poorly counterstained with cresyl violet. Abbreviations are as in other figures. Scale bar = 4 μm. (JPG 205 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, R., Zhang, X., Bian, F. et al. 3′UTR-Dependent Localization of a Purkinje Cell Messenger RNA in Dendrites. Cerebellum 7, 482–493 (2008). https://doi.org/10.1007/s12311-008-0051-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12311-008-0051-y

Keywords

Search

Navigation