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J. Biol. Chem., Vol. 283, Issue 9, 5918-5927, February 29, 2008

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Wnt-7a Modulates the Synaptic Vesicle Cycle and Synaptic Transmission in Hippocampal Neurons^*

Waldo Cerpa, Juan A. Godoy, Iván Alfaro, Ginny G. Farías, María J. Metcalfe, Rodrigo Fuentealba, Christian Bonansco, and Nibaldo C. Inestrosa¹

From the 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 and Departamento de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Av. Gran Bretaña 1111, 2360102 Valparaíso, Chile

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.

Received for publication, July 20, 2007 , and in revised form, December 18, 2007.

^* This work was supported by Fondo de Estudios Avanzados en Areas Prioritarias and Millennium Institute (El Instituto Milenio de Biología Fundamental y Aplicada) (to N. C. I.), Fondo Nacional de Ciencia y Tecnologia (Fondecyt) Grant 1061074 and DIPUV-REG 08/2005 grants (to C. B.), and predoctoral fellowships from Fondecyt (to W. C., I. A., and G. G. F.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1.

¹ To whom correspondence should be addressed: CRCP-Biomedical Center, Pontificia Universidad Católica de Chile, Alameda 340, 8331010 Santiago, Chile. Tel.: 56-2-686-2724/2720; Fax: 56-2-686-2959; E-mail: ninestrosa{at}bio.puc.cl.

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				G. G. Farias, I. E. Alfaro, W. Cerpa, C. P. Grabowski, J. A. Godoy, C. Bonansco, and N. C. Inestrosa Wnt-5a/JNK Signaling Promotes the Clustering of PSD-95 in Hippocampal Neurons J. Biol. Chem., June 5, 2009; 284(23): 15857 - 15866. [Abstract] [Full Text] [PDF]