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Characterization of Meteorin—An Evolutionary Conserved Neurotrophic Factor

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Abstract

Growth factors control cellular growth, proliferation, and differentiation and may have therapeutic applications. In this study, we focus on Meteorin which is a member of a largely uncharacterized evolutionary conserved two-member growth factor family. Our analysis shows that Meteorin is expressed in the central nervous system both during development and in adult mice. Detailed immunohistological analysis of the adult mouse brain reveals that Meteorin is highly expressed in Bergmann glia and in a few discrete neuronal populations residing in the superior colliculus, the ocular motor nucleus, the raphe and pontine nuclei, and in various thalamic nuclei. In addition, low levels of Meteorin is found in astrocytes (S100β+, OX42−) distributed ubiquitously throughout the brain. Meteorin was cloned and recombinant protein purified allowing N-terminal sequencing and mass spectrometric analysis showing that Meteorin is secreted as an unmodified monomer. This form is bioactive as it induces neurite outgrowth from dorsal root ganglions in vitro. Intrastriatal protein injection and lentiviral studies in vivo showed that Meteorin is a highly diffusible molecule in the brain and cellular uptake is apparent in specific populations which may carry the receptor. In summary, we provide a comprehensive expression analysis and have made and thoroughly validated molecular tools to help investigate the therapeutic potential of Meteorin.

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Abbreviations

5HT:

5-Hydroxytryptamine

CDNF:

Conserved dopamine neurotrophic factor

ChAT:

Choline acetyltransferase

ESI-MS:

Electrospray ionization mass spectrometry

GDNF:

Glial-derived neurotrophic factor

GFAP:

Glial fibrillary acidic protein

IHC:

Immunohistochemistry

ISH:

In situ hybridization

LC-ESI-MS/MS:

Liquid chromatography electrospray ionization tandem mass spectrometry

MALDI-TOF:

Matrix-assisted laser desorption/ionization time-of-flight

METRN:

Meteorin, glial cell differentiation regulator

NGF:

Nerve growth factor

RP:

Reverse phase

SC:

Superior colliculus

References

  • Bendtsen, J. D., Nielsen, H., von Heijne, G., & Brunak, S. (2004). Improved prediction of signal peptides: SignalP 3.0. Journal of Molecular Biology, 340, 783–795. doi:10.1016/j.jmb.2004.05.028.

    Article  PubMed  CAS  Google Scholar 

  • Ekestern, E. (2004). Neurotrophic factors and amyotrophic lateral sclerosis. Neuro-Degenerative Diseases, 1, 88–100. doi:10.1159/000080049.

    PubMed  CAS  Google Scholar 

  • Evans, J. R., & Barker, R. A. (2008). Neurotrophic factors as a therapeutic target for Parkinson's disease. Expert Opinion on Therapeutic Targets, 12, 437–447. doi:10.1517/14728222.12.4.437.

    Article  PubMed  CAS  Google Scholar 

  • Hamilton, J. F., Morrison, P. F., Chen, M. Y., Harvey-White, J., Pernaute, R. S., Phillips, H., et al. (2001). Heparin coinfusion during convection-enhanced delivery (CED) increases the distribution of the glial-derived neurotrophic factor (GDNF) ligand family in rat striatum and enhances the pharmacological activity of neurturin. Experimental Neurology, 168, 155–161. doi:10.1006/exnr.2000.7571.

    Article  PubMed  CAS  Google Scholar 

  • Jensen, M. L., Timmermann, D. B., Johansen, T. H., Schousboe, A., Varming, T., & Ahring, P. K. (2002). The beta subunit determines the ion selectivity of the GABAA receptor. The Journal of Biological Chemistry, 277, 41438–41447. doi:10.1074/jbc.M205645200.

    Article  PubMed  CAS  Google Scholar 

  • Jorgensen, J. R., Juliusson, B., Henriksen, K. F., Hansen, C., Knudsen, S., Petersen, T. N., et al. (2006). Identification of novel genes regulated in the developing human ventral mesencephalon. Experimental Neurology, 198, 427–437. doi:10.1016/j.expneurol.2005.12.023.

    Article  PubMed  CAS  Google Scholar 

  • Leander, J. J., Dago, L., Tornoe, J., Rosenblad, C., & Kusk, P. (2005). A new versatile and compact lentiviral vector. Molecular Biotechnology, 29, 47–56. doi:10.1385/MB:29:1:47.

    Article  Google Scholar 

  • Lein, E. S., et al. (2007). Genome-wide atlas of gene expression in the adult mouse brain. Nature, 445, 168–176. doi:10.1038/nature05453.

    Article  PubMed  CAS  Google Scholar 

  • Lindholm, P., Voutilainen, M. H., Lauren, J., Peranen, J., Leppanen, V. M., Andressoo, J. O., et al. (2007). Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo. Nature, 448, 73–77. doi:10.1038/nature05957.

    Article  PubMed  CAS  Google Scholar 

  • Lindvall, O., & Wahlberg, L. U. (2008). Encapsulated cell biodelivery of GDNF: A novel clinical strategy for neuroprotection and neuroregeneration in Parkinson's disease. Experimental Neurology, 209, 82–88. doi:10.1016/j.expneurol.2007.08.019.

    Article  PubMed  CAS  Google Scholar 

  • Nakari-Setala, T., Aro, N., Kalkkinen, N., Alatalo, E., & Penttila, M. (1996). Genetic and biochemical characterization of the Trichoderma reesei hydrophobin HFBI. European Journal of Biochemistry, 235, 248–255. doi:10.1111/j.1432-1033.1996.00248.x.

    Article  PubMed  CAS  Google Scholar 

  • Nishino, J., Yamashita, K., Hashiguchi, H., Fujii, H., Shimazaki, T., & Hamada, H. (2004). Meteorin: A secreted protein that regulates glial cell differentiation and promotes axonal extension. The EMBO Journal, 23, 1998–2008. doi:10.1038/sj.emboj.7600202.

    Article  PubMed  CAS  Google Scholar 

  • Park, J. A., Lee, H. S., Ko, K. J., Park, S. Y., Kim, J. H., Choe, G., et al. (2008). Meteorin regulates angiogenesis at the gliovascular interface. Glia, 56, 247–258. doi:10.1002/glia.20600.

    Article  PubMed  Google Scholar 

  • Poutanen, M., Salusjarvi, L., Ruohonen, L., Penttila, M., & Kalkkinen, N. (2001). Use of matrix-assisted laser desorption/ionization time-of-flight mass mapping and nanospray liquid chromatography/electrospray ionization tandem mass spectrometry sequence tag analysis for high sensitivity identification of yeast proteins separated by two-dimensional gel electrophoresis. Rapid Communications in Mass Spectrometry, 15, 1685–1692. doi:10.1002/rcm.424.

    Article  PubMed  CAS  Google Scholar 

  • Schindowski, K., Belarbi, K., & Buee, L. (2008). Neurotrophic factors in Alzheimer's disease: Role of axonal transport. Genes Brain & Behavior, 7(Suppl 1), 43–56.

    Article  CAS  Google Scholar 

  • Shevchenko, A., Wilm, M., Vorm, O., & Mann, M. (1996). Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Analytical Chemistry, 68, 850–858. doi:10.1021/ac950914h.

    Article  PubMed  CAS  Google Scholar 

  • Slemmon, J. R., Danho, W., Hempstead, J. L., & Morgan, J. I. (1985). Cerebellin: A quantifiable marker for Purkinje cell maturation. Proceedings of the National Academy of Sciences of the United States of America, 82, 7145–7148. doi:10.1073/pnas.82.20.7145.

    Article  PubMed  CAS  Google Scholar 

  • Sun, P. D., & Davies, D. R. (1995). The cystine-knot growth-factor superfamily. Annual Review of Biophysics and Biomolecular Structure, 24, 269–291. doi:10.1146/annurev.bb.24.060195.001413.

    Article  PubMed  CAS  Google Scholar 

  • Thompson, L., Barraud, P., Andersson, E., Kirik, D., & Bjorklund, A. (2005). Identification of dopaminergic neurons of nigral and ventral tegmental area subtypes in grafts of fetal ventral mesencephalon based on cell morphology, protein expression, and efferent projections. The Journal of Neuroscience, 25, 6467–6477. doi:10.1523/JNEUROSCI.1676-05.2005.

    Article  PubMed  CAS  Google Scholar 

  • Tuszynski, M. H. (2007). Nerve growth factor gene delivery: Animal models to clinical trials. Developmental Neurobiology, 67, 1204–1215. doi:10.1002/dneu.20510.

    Article  PubMed  CAS  Google Scholar 

  • Ylonen, A., Rinne, A., Herttuainen, J., Bogwald, J., Jarvinen, M., & Kalkkinen, N. (1999). Atlantic salmon (Salmo salar L.) skin contains a novel kininogen and another cysteine proteinase inhibitor. European Journal of Biochemistry, 266, 1066–1072. doi:10.1046/j.1432-1327.1999.00950.x.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the EU project EuroStemCell (LSHBCT-2003-503005). The Wilhelm Johannsen Centre for Functional Genome Research is established by the Danish National Research Foundation. CKR is supported by Danish Stem Cell Research Doctoral School (DASCDOC). The authors would like to thank Birgitte Romme Larsen, Sanne Tine Asnæs, Hanne Fosmark, Anne Klit Thomsen, Gunilla Rönnholm, and Karen Friis Henriksen for excellent technical assistance and Bengt Mattsson for preparing the illustration of intrastriatal injection in Fig. 6.

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Authors and Affiliations

  1. NsGene A/S, Baltorpvej 154, 2750, Ballerup, Denmark

    Jesper Roland Jørgensen, Lone Fjord-Larsen, Christina Krabbe, Malene Torp & Lars Wahlberg

  2. Wallenberg Neuroscience Center, Department of Experimental Medical Research, Lund University, 221 84, Lund, Sweden

    Lachlan Thompson

  3. Anatomy & Neurobiology, University of Southern Denmark, Winsløwparken 21, 5000, Odense, Denmark

    Christina Krabbe

  4. Institute of Biotechnology, Protein Chemistry Research Group, University of Helsinki, 00014, Helsinki, Finland

    Nisse Kalkkinen

  5. The Wilhelm Johannsen Centre for Functional Genome Research, IMBG, Panum Institute, University of Copenhagen, 2200, Copenhagen, Denmark

    Claus Hansen

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  1. Jesper Roland Jørgensen
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  2. Lachlan Thompson
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Correspondence to Jesper Roland Jørgensen.

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Jørgensen, J.R., Thompson, L., Fjord-Larsen, L. et al. Characterization of Meteorin—An Evolutionary Conserved Neurotrophic Factor. J Mol Neurosci 39, 104–116 (2009). https://doi.org/10.1007/s12031-009-9189-4

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  • DOI: https://doi.org/10.1007/s12031-009-9189-4

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