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Glutamatergic cerebellar granule neurons synthesize and secrete reelin in vitro

Published online by Cambridge University Press:  13 August 2009

Mélanie Sinagra ,
Cecilia Gonzalez Campo ,
Danièle Verrier ,
Olivier Moustié ,
Olivier J. Manzoni  and
Pascale Chavis
Mélanie Sinagra
Affiliation:
INSERM U862, Neurocentre Magendie, Pathophysiology of Synaptic Plasticity, 146 rue Léo Saignat, Bordeaux, F-33000, France Université de Bordeaux, Bordeaux, F-33000, France
Cecilia Gonzalez Campo
Affiliation:
INSERM U862, Neurocentre Magendie, Pathophysiology of Synaptic Plasticity, 146 rue Léo Saignat, Bordeaux, F-33000, France Université de Bordeaux, Bordeaux, F-33000, France
Danièle Verrier
Affiliation:
INSERM U862, Neurocentre Magendie, Pathophysiology of Synaptic Plasticity, 146 rue Léo Saignat, Bordeaux, F-33000, France Université de Bordeaux, Bordeaux, F-33000, France
Olivier Moustié
Affiliation:
INSERM U862, Neurocentre Magendie, Pathophysiology of Synaptic Plasticity, 146 rue Léo Saignat, Bordeaux, F-33000, France
Olivier J. Manzoni
Affiliation:
INSERM U862, Neurocentre Magendie, Pathophysiology of Synaptic Plasticity, 146 rue Léo Saignat, Bordeaux, F-33000, France Université de Bordeaux, Bordeaux, F-33000, France
Pascale Chavis*
Affiliation:
INSERM U862, Neurocentre Magendie, Pathophysiology of Synaptic Plasticity, 146 rue Léo Saignat, Bordeaux, F-33000, France Université de Bordeaux, Bordeaux, F-33000, France
*
Correspondence should be addressed to: Pascale Chavis, INSERM U862, Neurocentre Magendie, Pathophysiology of Synaptic Plasticity, 146 rue Léo Saignat, Bordeaux, F-33000, France phone: (+33) 5 57573771 email: [email protected]
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Abstract

In the postnatal forebrain, the extracellular matrix protein reelin is expressed and secreted by subsets of GABAergic neurons, whereas in the cerebellum reelin is detected in glutamatergic cells of the granule cell layer. Thus, various regions of the postnatal brain present different patterns of reelin expression, whose significance remains unknown. We combined immunocytochemical and pharmacological approaches to characterize the phenotypic and temporal profiles of reelin expression in dissociated cultures of cerebellar granule neurons. A single type of reelin immunoreactivity, identified by a punctate labelling, was present in the somata of the majority of neurons. This immunoreactivity was observed throughout maturation and was exclusively present in glutamatergic neurons expressing the vesicular glutamate transporter 1. Neurons containing the reelin receptors apolipoprotein E receptor 2 (Apoer2) and very low-density lipoprotein receptor (Vldlr) represented about 80% of cerebellar neurons. The vast majority of reelin-positive neurons coexpressed Apoer2, suggesting that reelin immunoreactivity resulted in part from receptor-bound reelin. Inhibition of protein synthesis with cycloheximide completely abolished reelin immunoreactivity. In contrast, blocking protein secretion with brefeldin A did not affect the proportion of punctate neurons but revealed a subpopulation of neurons characterized by a solid reelin staining. These data show for the first time that a homogeneous population of glutamatergic neurons can synthesize and secrete reelin in cerebellar granule cells in vitro.

Keywords

Reelinextracellular matrixglutamatergic neuronssecretioncerebellar granule cells
Type
Research Article
Information
Neuron Glia Biology , Volume 4 , Special Issue 3: Cell Adhesion and Extracellular Matrix Molecules in Synaptic Plasticity , August 2008 , pp. 189 - 196
Copyright
Copyright © Cambridge University Press 2009

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References

REFERENCES

Alcantara, S., Ruiz, M., D'Arcangelo, G., Ezan, F., de Lecea, L., Curran, T. et al. (1998) Regional and cellular patterns of reelin mRNA expression in the forebrain of the developing and adult mouse. Journal of Neuroscience 18, 7779–7799.CrossRefGoogle ScholarPubMed
Clatworthy, A.E., Stockinger, W., Christie, R.H., Schneider, W.J., Nimpf, J., Hyman, B.T. et al. (1999) Expression and alternate splicing of apolipoprotein E receptor 2 in brain. Neuroscience 90, 903–911.CrossRefGoogle ScholarPubMed
D'Arcangelo, G., Homayouni, R., Keshvara, L., Rice, D.S., Sheldon, M. and Curran, T. (1999) Reelin is a ligand for lipoprotein receptors. Neuron 24, 471–479.CrossRefGoogle ScholarPubMed
D'Arcangelo, G., Miao, G.G., Chen, S.C., Soares, H.D., Morgan, J.I. and Curran, T. (1995) A protein related to extracellular matrix proteins deleted in the mouse mutant reeler. Nature 374, 719–723.CrossRefGoogle ScholarPubMed
De, A., Krueger, J.M. and Simasko, S.M. (2003) Tumor necrosis factor alpha increases cytosolic calcium responses to AMPA and KCl in primary cultures of rat hippocampal neurons. Brain Research 981, 133–142.CrossRefGoogle ScholarPubMed
del Rio, J.A., Martinez, A., Fonseca, M., Auladell, C. and Soriano, E. (1995) Glutamate-like immunoreactivity and fate of Cajal-Retzius cells in the murine cortex as identified with calretinin antibody. Cerebral Cortex 5, 13–21.CrossRefGoogle ScholarPubMed
Derer, P. and Derer, M. (1990) Cajal-Retzius cell ontogenesis and death in mouse brain visualized with horseradish peroxidase and electron microscopy. Neuroscience 36, 839–856.CrossRefGoogle ScholarPubMed
Derer, P., Derer, M. and Goffinet, A. (2001) Axonal secretion of Reelin by Cajal-Retzius cells: evidence from comparison of normal and Reln(Orl) mutant mice. Journal of Comparative Neurology 440, 136–143.CrossRefGoogle ScholarPubMed
Drakew, A., Frotscher, M., Deller, T., Ogawa, M. and Heimrich, B. (1998) Developmental distribution of a reeler gene-related antigen in the rat hippocampal formation visualized by CR-50 immunocytochemistry. Neuroscience 82, 1079–1086.CrossRefGoogle ScholarPubMed
Gonzalez Campo, C., Sinagra, M., Verrier, D., Manzoni, O.J. and Chavis, P. (2009) Reelin secreted by GABAergic neurons regulates glutamate receptor homeostasis. PloS ONE 4, e5505.CrossRefGoogle Scholar
Groc, L., Choquet, D., Stephenson, F.A., Verrier, D., Manzoni, O.J. and Chavis, P. (2007) NMDA receptor surface trafficking and synaptic subunit composition are developmentally regulated by the extracellular matrix protein Reelin. Journal of Neuroscience 27, 10165–10175.CrossRefGoogle ScholarPubMed
Hallberg, O.E., Bogen, I.L., Reistad, T., Haug, K.H., Wright, M.S., Fonnum, F. et al. (2006) Differential development of vesicular glutamate transporters in brain: an in vitro study of cerebellar granule cells. Neurochemistry International 48, 579–585.CrossRefGoogle Scholar
Herz, J. and Chen, Y. (2006) Reelin, lipoprotein receptors and synaptic plasticity. Nature Reviews Neuroscience 7, 850–859.CrossRefGoogle ScholarPubMed
Hevner, R.F., Neogi, T., Englund, C., Daza, R.A. and Fink, A. (2003) Cajal-Retzius cells in the mouse: transcription factors, neurotransmitters, and birthdays suggest a pallial origin. Brain Research Developmental Brain Research 141, 39–53.CrossRefGoogle ScholarPubMed
Hibi, T., Mizutani, M., Baba, A. and Hattori, M. (2009) Splicing variations in the ligand-binding domain of ApoER2 results in functional differences in the binding properties to Reelin. Neuroscience Research 63, 251–258.CrossRefGoogle ScholarPubMed
Ikeda, Y. and Terashima, T. (1997) Expression of reelin, the gene responsible for the reeler mutation, in embryonic development and adulthood in the mouse. Developmental Dynamics 210, 157–172.3.0.CO;2-F>CrossRefGoogle ScholarPubMed
Ina, A., Sugiyama, M., Konno, J., Yoshida, S., Ohmomo, H., Nogami, H. et al. (2007) Cajal-Retzius cells and subplate neurons differentially express vesicular glutamate transporters 1 and 2 during development of mouse cortex. European Journal of Neuroscience 26, 615–623.CrossRefGoogle ScholarPubMed
Kim, D.H., Iijima, H., Goto, K., Sakai, J., Ishii, H., Kim, H.J. et al. (1996) Human apolipoprotein E receptor 2. A novel lipoprotein receptor of the low density lipoprotein receptor family predominantly expressed in brain. Journal of Biological Chemistry 271, 8373–8380.CrossRefGoogle ScholarPubMed
Lacor, P.N., Grayson, D.R., Auta, J., Sugaya, I., Costa, E. and Guidotti, A. (2000) Reelin secretion from glutamatergic neurons in culture is independent from neurotransmitter regulation. Proceedings of the National Academy of Sciences of the U.S.A. 97, 3556–3561.CrossRefGoogle ScholarPubMed
Lippincott-Schwartz, J., Donaldson, J.G., Schweizer, A., Berger, E.G., Hauri, H.P., Yuan, L.C. et al. (1990) Microtubule-dependent retrograde transport of proteins into the ER in the presence of brefeldin A suggests an ER recycling pathway. Cell 60, 821–836.CrossRefGoogle Scholar
Martinez-Cerdeno, V., Galazo, M.J., Cavada, C. and Clasca, F. (2002) Reelin immunoreactivity in the adult primate brain: intracellular localization in projecting and local circuit neurons of the cerebral cortex, hippocampus and subcortical regions. Cerebral Cortex 12, 1298–1311.CrossRefGoogle ScholarPubMed
Martinez-Cerdeno, V., Galazo, M.J. and Clasca, F. (2003) Reelin-immunoreactive neurons, axons, and neuropil in the adult ferret brain: evidence for axonal secretion of reelin in long axonal pathways. Journal of Comparative Neurology 463, 92–116.CrossRefGoogle ScholarPubMed
Miyata, T., Nakajima, K., Aruga, J., Takahashi, S., Ikenaka, K., Mikoshiba, K. et al. (1996) Distribution of a reeler gene-related antigen in the developing cerebellum: an immunohistochemical study with an allogeneic antibody CR-50 on normal and reeler mice. Journal of Comparative Neurology 372, 215–228.3.0.CO;2-6>CrossRefGoogle ScholarPubMed
Ogawa, M., Miyata, T., Nakajima, K., Yagyu, K., Seike, M., Ikenaka, K. et al. (1995) The reeler gene-associated antigen on Cajal-Retzius neurons is a crucial molecule for laminar organization of cortical neurons. Neuron 14, 899–912.CrossRefGoogle ScholarPubMed
Perez-Garcia, C.G., Tissir, F., Goffinet, A.M. and Meyer, G. (2004) Reelin receptors in developing laminated brain structures of mouse and human. European Journal of Neuroscience 20, 2827–2832.CrossRefGoogle ScholarPubMed
Pesold, C., Impagnatiello, F., Pisu, M.G., Uzunov, D.P., Costa, E., Guidotti, A. et al. (1998) Reelin is preferentially expressed in neurons synthesizing gamma-aminobutyric acid in cortex and hippocampus of adult rats. Proceedings of the National Academy of Sciences of the U.S.A. 95, 3221–3226.CrossRefGoogle ScholarPubMed
Ramos-Moreno, T., Galazo, M.J., Porrero, C., Martinez-Cerdeno, V. and Clasca, F. (2006) Extracellular matrix molecules and synaptic plasticity: immunomapping of intracellular and secreted Reelin in the adult rat brain. European Journal of Neuroscience 23, 401–422.CrossRefGoogle ScholarPubMed
Schiffmann, S.N., Bernier, B. and Goffinet, A.M. (1997) Reelin mRNA expression during mouse brain development. European Journal of Neuroscience 9, 1055–1071.CrossRefGoogle ScholarPubMed
Sinagra, M., Verrier, D., Frankova, D., Korwek, K.M., Blahos, J., Weeber, E.J. et al. (2005) Reelin, very-low-density lipoprotein receptor, and apolipoprotein E receptor 2 control somatic NMDA receptor composition during hippocampal maturation in vitro. Journal of Neuroscience 25, 6127–6136.CrossRefGoogle ScholarPubMed
Tissir, F. and Goffinet, A.M. (2003) Reelin and brain development. Nature Reviews Neuroscience 4, 496–505.CrossRefGoogle ScholarPubMed
Weeber, E.J., Beffert, U., Jones, C., Christian, J.M., Forster, E., Sweatt, J.D. et al. (2002) Reelin and ApoE receptors cooperate to enhance hippocampal synaptic plasticity and learning. Journal of Biological Chemistry 277, 39944–39952.CrossRefGoogle ScholarPubMed