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

Lorena Varela-Nallar, Catalina P. Grabowski, Ivn E. Alfaro, Alejandra R. Alvarez, Nibaldo C. Inestrosa

Research output: Contribution to journalArticlepeer-review

92 Citations (Scopus)


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.

Original languageEnglish
Article number41
JournalNeural Development
Issue number1
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Developmental Neuroscience


Dive into the research topics of 'Role of the Wnt receptor Frizzled-1 in presynaptic differentiation and function'. Together they form a unique fingerprint.

Cite this