Frizzled-5 receptor is involved in neuronal polarity and morphogenesis of hippocampal neurons.
The Wnt signaling pathway plays important roles during different stages of neuronal development, including neuronal polarization and dendritic and axonal outgrowth. However, little is known about the identity of the Frizzled receptors mediating these processes. In the present study, we investigated...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3800132?pdf=render |
| _version_ | 1818298040705875968 |
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| author | Paula G Slater Valerie T Ramirez Christian Gonzalez-Billault Lorena Varela-Nallar Nibaldo C Inestrosa |
| author_facet | Paula G Slater Valerie T Ramirez Christian Gonzalez-Billault Lorena Varela-Nallar Nibaldo C Inestrosa |
| author_sort | Paula G Slater |
| collection | DOAJ |
| description | The Wnt signaling pathway plays important roles during different stages of neuronal development, including neuronal polarization and dendritic and axonal outgrowth. However, little is known about the identity of the Frizzled receptors mediating these processes. In the present study, we investigated the role of Frizzled-5 (Fzd5) on neuronal development in cultured Sprague-Dawley rat hippocampal neurons. We found that Fzd5 is expressed early in cultured neurons on actin-rich structures localized at minor neurites and axonal growth cones. At 4 DIV, Fzd5 polarizes 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 Fzd5 during the acquisition of neuronal polarity induces mislocalization of the receptor and a loss of polarized axonal markers. 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 of axons and increased total dendrite length and arborization. Fzd5 activated JNK in HEK293 cells and the effects triggered by Fzd5 overexpression in neurons were partially prevented by inhibition of JNK, suggesting that a non-canonical Wnt signaling mechanism might be involved. Our results suggest that, Fzd5 has a role in the establishment of neuronal polarity, and in the morphogenesis of neuronal processes, in part through the activation of the non-canonical Wnt mechanism involving JNK. |
| first_indexed | 2024-12-13T04:29:00Z |
| format | Article |
| id | doaj.art-95b04c0ca9124a4b97c46ea585bc1eaf |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T04:29:00Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-95b04c0ca9124a4b97c46ea585bc1eaf2022-12-21T23:59:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7889210.1371/journal.pone.0078892Frizzled-5 receptor is involved in neuronal polarity and morphogenesis of hippocampal neurons.Paula G SlaterValerie T RamirezChristian Gonzalez-BillaultLorena Varela-NallarNibaldo C InestrosaThe Wnt signaling pathway plays important roles during different stages of neuronal development, including neuronal polarization and dendritic and axonal outgrowth. However, little is known about the identity of the Frizzled receptors mediating these processes. In the present study, we investigated the role of Frizzled-5 (Fzd5) on neuronal development in cultured Sprague-Dawley rat hippocampal neurons. We found that Fzd5 is expressed early in cultured neurons on actin-rich structures localized at minor neurites and axonal growth cones. At 4 DIV, Fzd5 polarizes 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 Fzd5 during the acquisition of neuronal polarity induces mislocalization of the receptor and a loss of polarized axonal markers. 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 of axons and increased total dendrite length and arborization. Fzd5 activated JNK in HEK293 cells and the effects triggered by Fzd5 overexpression in neurons were partially prevented by inhibition of JNK, suggesting that a non-canonical Wnt signaling mechanism might be involved. Our results suggest that, Fzd5 has a role in the establishment of neuronal polarity, and in the morphogenesis of neuronal processes, in part through the activation of the non-canonical Wnt mechanism involving JNK.http://europepmc.org/articles/PMC3800132?pdf=render |
| spellingShingle | Paula G Slater Valerie T Ramirez Christian Gonzalez-Billault Lorena Varela-Nallar Nibaldo C Inestrosa Frizzled-5 receptor is involved in neuronal polarity and morphogenesis of hippocampal neurons. PLoS ONE |
| title | Frizzled-5 receptor is involved in neuronal polarity and morphogenesis of hippocampal neurons. |
| title_full | Frizzled-5 receptor is involved in neuronal polarity and morphogenesis of hippocampal neurons. |
| title_fullStr | Frizzled-5 receptor is involved in neuronal polarity and morphogenesis of hippocampal neurons. |
| title_full_unstemmed | Frizzled-5 receptor is involved in neuronal polarity and morphogenesis of hippocampal neurons. |
| title_short | Frizzled-5 receptor is involved in neuronal polarity and morphogenesis of hippocampal neurons. |
| title_sort | frizzled 5 receptor is involved in neuronal polarity and morphogenesis of hippocampal neurons |
| url | http://europepmc.org/articles/PMC3800132?pdf=render |
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