Role of the <it>Wnt </it>receptor Frizzled-1 in presynaptic differentiation and function
<p>Abstract</p> <p>Background</p> <p>The <it>Wnt </it>signaling pathway regulates several fundamental developmental processes and recently has been shown to be involved in different aspects of synaptic differentiation and plasticity. Some <it>Wnt </...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2009-11-01
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| Series: | Neural Development |
| Online Access: | http://www.neuraldevelopment.com/content/4/1/41 |
| _version_ | 1818389499071168512 |
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| author | Alvarez Alejandra R Alfaro Iván E Grabowski Catalina P Varela-Nallar Lorena Inestrosa Nibaldo C |
| author_facet | Alvarez Alejandra R Alfaro Iván E Grabowski Catalina P Varela-Nallar Lorena Inestrosa Nibaldo C |
| author_sort | Alvarez Alejandra R |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The <it>Wnt </it>signaling pathway regulates several fundamental developmental processes and recently has been shown to be involved in different aspects of synaptic differentiation and plasticity. Some <it>Wnt </it>signaling components are localized at central synapses, and it is thus possible that this pathway could be activated at the synapse.</p> <p>Results</p> <p>We examined the distribution of the <it>Wnt </it>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 <it>Wnt-3a </it>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 <it>Wnt-3a </it>was able to modulate the kinetics of neurotransmitter release.</p> <p>Conclusion</p> <p>Our results indicate that the activation of the <it>Wnt </it>pathway through Frizzled-1 occurs at the presynaptic level, and suggest that the synaptic effects of the <it>Wnt </it>signaling pathway could be modulated by local activation through synaptic Frizzled receptors.</p> |
| first_indexed | 2024-12-14T04:42:42Z |
| format | Article |
| id | doaj.art-0dc6c8cc5ad345619387c700f839ab53 |
| institution | Directory Open Access Journal |
| issn | 1749-8104 |
| language | English |
| last_indexed | 2024-12-14T04:42:42Z |
| publishDate | 2009-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Neural Development |
| spelling | doaj.art-0dc6c8cc5ad345619387c700f839ab532022-12-21T23:16:46ZengBMCNeural Development1749-81042009-11-01414110.1186/1749-8104-4-41Role of the <it>Wnt </it>receptor Frizzled-1 in presynaptic differentiation and functionAlvarez Alejandra RAlfaro Iván EGrabowski Catalina PVarela-Nallar LorenaInestrosa Nibaldo C<p>Abstract</p> <p>Background</p> <p>The <it>Wnt </it>signaling pathway regulates several fundamental developmental processes and recently has been shown to be involved in different aspects of synaptic differentiation and plasticity. Some <it>Wnt </it>signaling components are localized at central synapses, and it is thus possible that this pathway could be activated at the synapse.</p> <p>Results</p> <p>We examined the distribution of the <it>Wnt </it>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 <it>Wnt-3a </it>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 <it>Wnt-3a </it>was able to modulate the kinetics of neurotransmitter release.</p> <p>Conclusion</p> <p>Our results indicate that the activation of the <it>Wnt </it>pathway through Frizzled-1 occurs at the presynaptic level, and suggest that the synaptic effects of the <it>Wnt </it>signaling pathway could be modulated by local activation through synaptic Frizzled receptors.</p>http://www.neuraldevelopment.com/content/4/1/41 |
| spellingShingle | Alvarez Alejandra R Alfaro Iván E Grabowski Catalina P Varela-Nallar Lorena Inestrosa Nibaldo C Role of the <it>Wnt </it>receptor Frizzled-1 in presynaptic differentiation and function Neural Development |
| title | Role of the <it>Wnt </it>receptor Frizzled-1 in presynaptic differentiation and function |
| title_full | Role of the <it>Wnt </it>receptor Frizzled-1 in presynaptic differentiation and function |
| title_fullStr | Role of the <it>Wnt </it>receptor Frizzled-1 in presynaptic differentiation and function |
| title_full_unstemmed | Role of the <it>Wnt </it>receptor Frizzled-1 in presynaptic differentiation and function |
| title_short | Role of the <it>Wnt </it>receptor Frizzled-1 in presynaptic differentiation and function |
| title_sort | role of the it wnt it receptor frizzled 1 in presynaptic differentiation and function |
| url | http://www.neuraldevelopment.com/content/4/1/41 |
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