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Open Access Highly Accessed Research article

Role of the Wnt receptor Frizzled-1 in presynaptic differentiation and function

Lorena Varela-Nallar12, Catalina P Grabowski1, Iván E Alfaro1, Alejandra R Alvarez2 and Nibaldo C Inestrosa1*

Author Affiliations

1 Centro de Envejecimiento y Regeneración (CARE), Centro de Regulación Celular y Patología "Joaquín V Luco" (CRCP) and MIFAB, Chile

2 Laboratorio de Señalización Celular, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile

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Neural Development 2009, 4:41  doi:10.1186/1749-8104-4-41

Published: 2 November 2009

Abstract

Background

The Wnt signaling pathway regulates several fundamental developmental processes and recently has been shown to be involved in different aspects of synaptic differentiation and plasticity. Some Wnt signaling components are localized at central synapses, and it is thus possible that this pathway could be activated at the synapse.

Results

We examined the distribution of the Wnt receptor Frizzled-1 in cultured hippocampal neurons and determined that this receptor is located at synaptic contacts co-localizing with presynaptic proteins. Frizzled-1 was found in functional synapses detected with FM1-43 staining and in synaptic terminals from adult rat brain. Interestingly, overexpression of Frizzled-1 increased the number of clusters of Bassoon, a component of the active zone, while treatment with the extracellular cysteine-rich domain (CRD) of Frizzled-1 decreased Bassoon clustering, suggesting a role for this receptor in presynaptic differentiation. Consistent with this, treatment with the Frizzled-1 ligand Wnt-3a induced presynaptic protein clustering and increased functional presynaptic recycling sites, and these effects were prevented by co-treatment with the CRD of Frizzled-1. Moreover, in synaptically mature neurons Wnt-3a was able to modulate the kinetics of neurotransmitter release.

Conclusion

Our results indicate that the activation of the Wnt pathway through Frizzled-1 occurs at the presynaptic level, and suggest that the synaptic effects of the Wnt signaling pathway could be modulated by local activation through synaptic Frizzled receptors.