Frizzled-5 Receptor Is Involved in Neuronal Polarity and Morphogenesis of Hippocampal NeuronsReportar como inadecuado

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The Wnt signaling pathway plays important roles during different stages of neuronal development, including neuronalpolarization and dendritic and axonal outgrowth. However, little is known about the identity of the Frizzled receptorsmediating these processes. In the present study, we investigated the role of Frizzled-5 Fzd5 on neuronaldevelopment in cultured Sprague-Dawley rat hippocampal neurons. We found that Fzd5 is expressed early incultured neurons on actin-rich structures localized at minor neurites and axonal growth cones. At 4 DIV, Fzd5polarizes towards the axon, where its expression is detected mainly at the peripheral zone of axonal growth cones,with no obvious staining at dendrites; suggesting a role of Fzd5 in neuronal polarization. Overexpression of Fzd5during the acquisition of neuronal polarity induces mislocalization of the receptor and a loss of polarized axonalmarkers. Fzd5 knock-down leads to loss of axonal proteins, suggesting an impaired neuronal polarity. In contrast,overexpression of Fzd5 in neurons that are already polarized did not alter polarity, but decreased the total length ofaxons and increased total dendrite length and arborization. Fzd5 activated JNK in HEK293 cells and the effectstriggered by Fzd5 overexpression in neurons were partially prevented by inhibition of JNK, suggesting that a noncanonicalWnt signaling mechanism might be involved. Our results suggest that, Fzd5 has a role in the establishmentof neuronal polarity, and in the morphogenesis of neuronal processes, in part through the activation of the noncanonicalWnt mechanism involving JNK.Nota general

Artículo de publicación ISI

Autor: Slater, Paula G.; - Ramirez, Valerie T.; - Gonzalez Billault, Christian; - Varela Nallar, Lorena; - Inestrosa, Nibaldo C.; -



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