Cerpa Waldo, Godoy Juan A, Alfaro Iván, Farías Ginny G, Metcalfe María J, Fuentealba Rodrigo, Bonansco Christian, Inestrosa Nibaldo C
Centro de Regulación Celular y Patología Joaquín V. Luco, Instituto Milenio MIFAB, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Alameda 340, 8331010 Santiago, Chile
J Biol Chem. 2008 Feb 29;283(9):5918-27. doi: 10.1074/jbc.M705943200. Epub 2007 Dec 20.
Wnt signaling is essential for neuronal development and the maintenance of the developing nervous system. Recent studies indicated that Wnt signaling modulates long term potentiation in adult hippocampal slices. We report here that different Wnt ligands are present in hippocampal neurons of rat embryo and adult rat, including Wnt-4, -5a, -7a, and -11. Wnt-7a acts as a canonical Wnt ligand in rat hippocampal neurons, stimulates clustering of presynaptic proteins, and induces recycling and exocytosis of synaptic vesicles as studied by FM dyes. Wnt-3a has a moderate effect on recycling of synaptic vesicles, and no effect of Wnt-1 and Wnt-5a was detected. Electrophysiological analysis on adult rat hippocampal slices indicates that Wnt-7a, but not Wnt-5a, increases neurotransmitter release in CA3-CA1 synapses by decreasing paired pulse facilitation and increasing the miniature excitatory post-synaptic currents frequency. These results indicate that the presynaptic function of rat hippocampal neurons is modulated by the canonical Wnt signaling.
Wnt信号通路对于神经元发育以及发育中的神经系统的维持至关重要。最近的研究表明，Wnt信号通路可调节成年海马切片中的长时程增强。我们在此报告，不同的Wnt配体存在于大鼠胚胎和成年大鼠的海马神经元中，包括Wnt-4、-5a、-7a和-11。Wnt-7a在大鼠海马神经元中作为典型的Wnt配体发挥作用，刺激突触前蛋白的聚集，并如通过FM染料所研究的那样诱导突触小泡的再循环和胞吐作用。Wnt-3a对突触小泡的再循环有中等程度的影响，未检测到Wnt-1和Wnt-5a有作用。对成年大鼠海马切片的电生理分析表明，Wnt-7a而非Wnt-5a通过降低双脉冲易化并增加微小兴奋性突触后电流频率来增加CA3-CA1突触中的神经递质释放。这些结果表明，大鼠海马神经元的突触前功能受典型Wnt信号通路调节。
