The Adhesion-GPCR BAI1 Regulates Synaptogenesis by Controlling the Recruitment of the Par3/Tiam1 Polarity Complex to Synaptic Sites

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dc.citation.firstpage6964en_US
dc.citation.issueNumber16en_US
dc.citation.journalTitleThe Journal of Neuroscienceen_US
dc.citation.lastpage6978en_US
dc.citation.volumeNumber33en_US
dc.contributor.authorDuman, Joseph G.en_US
dc.contributor.authorTzeng, Christopher P.en_US
dc.contributor.authorTu, Yen-Kueien_US
dc.contributor.authorMunjal, Tinaen_US
dc.contributor.authorSchwechter, Brandonen_US
dc.contributor.authorHo, Tammy Szu-Yuen_US
dc.contributor.authorTolias, Kimberley F.en_US
dc.contributor.orgBiosciencesen_US
dc.date.accessioned2013-05-02T16:14:27Zen_US
dc.date.available2014-05-03T05:10:04Zen_US
dc.date.issued2013en_US
dc.description.abstractExcitatory synapses are polarized structures that primarily reside on dendritic spines in the brain. The small GTPase Rac1 regulates the development and plasticity of synapses and spines by modulating actin dynamics. By restricting the Rac1-guanine nucleotide exchange factor Tiam1 to spines, the polarity protein Par3 promotes synapse development by spatially controlling Rac1 activation. However, the mechanism for recruiting Par3 to spines is unknown. Here, we identify brain-specific angiogenesis inhibitor 1 (BAI1) as a synaptic adhesion GPCR that is required for spinogenesis and synaptogenesis in mice and rats. We show that BAI1 interacts with Par3/Tiam1 and recruits these proteins to synaptic sites. BAI1 knockdown results in Par3/Tiam1 mislocalization and loss of activated Rac1 and filamentous actin from spines. Interestingly, BAI1 also mediates Rac-dependent engulfment in professional phagocytes through its interaction with a different Rac1-guanine nucleotide exchange factor module, ELMO/DOCK180. However, this interaction is dispensable for BAI1’s role in synapse development because a BAI1 mutant that cannot interact with ELMO/DOCK180 rescues spine defects in BAI1-knockdown neurons, whereas a mutant that cannot interact with Par3/Tiam1 rescues neither spine defects nor Par3 localization. Further, overexpression of Tiam1 rescues BAI1 knockdown spine phenotypes. These results indicate that BAI1 plays an important role in synaptogenesis that is mechanistically distinct from its role in phagocytosis. Furthermore, our results provide the first example of a cell surface receptor that targets members of the PAR polarity complex to synapses.en_US
dc.embargo.terms1 yearen_US
dc.identifier.citationDuman, Joseph G., Tzeng, Christopher P., Tu, Yen-Kuei, et al.. "The Adhesion-GPCR BAI1 Regulates Synaptogenesis by Controlling the Recruitment of the Par3/Tiam1 Polarity Complex to Synaptic Sites." <i>The Journal of Neuroscience,</i> 33, no. 16 (2013) 6964-6978. http://dx.doi.org/10.1523/JNEUROSCI.3978-12.2013.en_US
dc.identifier.doihttp://dx.doi.org/10.1523/JNEUROSCI.3978-12.2013en_US
dc.identifier.urihttps://hdl.handle.net/1911/71082en_US
dc.language.isoengen_US
dc.publisherThe Society for Neuroscienceen_US
dc.titleThe Adhesion-GPCR BAI1 Regulates Synaptogenesis by Controlling the Recruitment of the Par3/Tiam1 Polarity Complex to Synaptic Sitesen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
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