Semaphorin3A regulates synaptic function of differentiated hippocampal neurons.
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.
Bouzioukh
Farima
F
NMDA UMR CNRS 6156, IBDM, Université de la Méditerranée, Parc Scientifique de Luminy, CASE 901 13288 Marseille cedex 9, France.
Daoudal
Gaël
G
Falk
Julien
J
Debanne
Dominique
D
Rougon
Geneviève
G
Castellani
Valérie
V
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D000076122:Disks Large Homolog 4 Protein; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D051528:Guanylate Kinases; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D039942:Neuropilin-1 / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D040121:Semaphorin-3A / Q000494:pharmacology / Q000502:physiology*; D018709:Statistics, Nonparametric; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors; D014162:Transfection / Q000379:methods
D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D040121:Semaphorin-3A; D016708:Synaptophysin; D039942:Neuropilin-1; D048052:Mitogen-Activated Protein Kinase 3; D051528:Guanylate Kinases; D010751:Phosphopyruvate Hydratase