Bouzioukh Farima, Daoudal Gaël, Falk Julien, Debanne Dominique, Rougon Geneviève, Castellani Valérie
NMDA UMR CNRS 6156, IBDM, Université de la Méditerranée, Parc Scientifique de Luminy, CASE 901 13288 Marseille cedex 9, France.
Eur J Neurosci. 2006 May;23(9):2247-54. doi: 10.1111/j.1460-9568.2006.04783.x.
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.
信号素是发育中神经元突起的主要化学排斥因子。它们在成年阶段的持续表达表明，它们可能对神经回路的功能有贡献。我们研究了成年海马神经元中信号素3A（Sema3A）的功能特性，并报告说，外源性应用这种信号会降低海马切片CA1区诱发的突触传递效率。原位杂交、成像和生化技术表明，Sema3A受体成分神经纤毛蛋白-1存在于海马突触中，并定位于突触前膜。在分化的培养海马神经元中，Sema3A在胞体和神经突区域引起Erk1/2磷酸化。此外，应用Sema3A导致突触素和突触后致密物95斑点显著减少，而不影响轴突直径。这些观察结果揭示了分泌信号素的新功能潜力，这表明这些信号可能调节成人大脑中突触的形态和功能。
