期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 291, 期 36, 页码 19092-19107出版社
ELSEVIER
DOI: 10.1074/jbc.M116.722132
关键词
-
资金
- FONDECYT [1120156, 1160724]
- Basal Center of Excellence in Science and Technology [CONICYT-PFB12/2007]
- CONICYT [3140355]
Wnt ligands play crucial roles in the development and regulation of synapse structure and function. Specifically, Wnt-5a acts as a secreted growth factor that regulates dendritic spine formation in rodent hippocampal neurons, resulting in postsynaptic development that promotes the clustering of the PSD-95 (postsynaptic density protein 95). Here, we focused on the early events occurring after the interaction between Wnt-5a and its Frizzled receptor at the neuronal cell surface. Additionally, we studied the role of heterotrimeric G proteins in Wnt-5a-dependent synaptic development. We report that FZD9 (Frizzled9), a Wnt receptor related to Williams syndrome, is localized in the postsynaptic region, where it interacts with Wnt-5a. Functionally, FZD9 is required for the Wnt-5a-mediated increase in dendritic spine density. FZD9 forms a precoupled complex with G alpha(o) under basal conditions that dissociates after Wnt-5a stimulation. Accordingly, we found that G protein inhibition abrogates the Wnt-5a-dependent pathway in hippocampal neurons. In particular, the activation of G alpha(o) appears to be a key factor controlling the Wnt-5a-induced dendritic spine density. In addition, we found that G beta gamma is required for the Wnt-5a-mediated increase in cytosolic calcium levels and spinogenesis. Our findings reveal that FZD9 and heterotrimeric G proteins regulate Wnt-5a signaling and dendritic spines in cultured hippocampal neurons.
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