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Semaphorin3A regulates synaptic function of differentiated hippocampal neurons

Authors

  • Farima Bouzioukh,

    1. NMDA UMR CNRS 6156, IBDM, Université de la Méditerranée, Parc Scientifique de Luminy, CASE 901 13288 Marseille cedex 9, France
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    • *

      Present address: Department of Molecular Neurobiology, Max-Planck Institute of Neurobiology Am Klopferspitz 18, 82152 Munich-Martinsried, Germany.

  • Gaël Daoudal,

    1. Neurobiologie des Canaux Ioniques, INSERM UMR 641 I.F.R. Jean Roche, Faculté de Médecine, secteur Nord Boulevard P. Dramard 13916 Marseille Cedex 20, France
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  • Julien Falk,

    1. CGMC UMR CNRS 5534 Université C. Bernard, 43 Bd du 11 Novembre 1918, 69622 Villeurbanne, France
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  • Dominique Debanne,

    1. Neurobiologie des Canaux Ioniques, INSERM UMR 641 I.F.R. Jean Roche, Faculté de Médecine, secteur Nord Boulevard P. Dramard 13916 Marseille Cedex 20, France
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  • Geneviève Rougon,

    1. NMDA UMR CNRS 6156, IBDM, Université de la Méditerranée, Parc Scientifique de Luminy, CASE 901 13288 Marseille cedex 9, France
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  • Valérie Castellani

    1. NMDA UMR CNRS 6156, IBDM, Université de la Méditerranée, Parc Scientifique de Luminy, CASE 901 13288 Marseille cedex 9, France
    2. CGMC UMR CNRS 5534 Université C. Bernard, 43 Bd du 11 Novembre 1918, 69622 Villeurbanne, France
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Dr V. Castellani, as above.
E-mail: castellani@cgmc.univ-lyon1.fr

Abstract

Semaphorins are major chemorepellents for developing neuronal projections. Their persistent expression at adult stages suggests that they may contribute to the functioning of neuronal circuits. We investigated the functional properties of semaphorin3A (Sema3A) in adult hippocampal neurons, and report that exogenous application of this cue decreases the efficacy of synaptic transmission evoked in the CA1 region of hippocampal slices. In situ hybridization, imaging and biochemical techniques showed that the Sema3A receptor component neuropilin-1 is present at hippocampal synapses and localizes in the presynaptic membrane. In differentiated cultured hippocampal neurons, Sema3A elicited Erk1/2 phosphorylation in somata and neuritic compartments. Furthermore, Sema3A application resulted in a striking reduction of synaptophysin and postsynaptic density 95 puncta without affecting the axon diameter. These observations reveal novel functional potentialities for secreted semaphorins, which suggest that these cues could modulate the morphology and function of synapses in the adult brain.

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