Further, cultured neurons treated with the type 1 mGluR (mGluR1 and mGluR5) agonist 3,5-dihydroxyphenylglycine (DHPG) exhibit increased dendrite growth during early development ( Cruz-Martín et al., 2012). ![]() Both hippocampal and cortical neurons of mice lacking Grm5, the gene that encodes the glutamate receptor mGluR5, develop significantly less complex dendritic arbors than controls in vivo ( Ballester-Rosado et al., 2010 Loerwald et al., 2015). ![]() Cultured primary hippocampal neurons treated with glutamate develop significantly more complex dendritic arbors when compared with controls, whereas blocking activity of glutamate receptors results in the formation of less complex dendritic arbors ( Charych et al., 2006 Hamad et al., 2011 Previtera and Firestein, 2015). Namely, the neurotransmitter glutamate has been strongly implicated in the establishment of dendritic morphology ( Portera-Cailliau et al., 2003 Park et al., 2007 Ballester-Rosado et al., 2010). We thus reveal a “phospho-switch” within delta-catenin, subject to a glutamate-mediated signaling pathway, that assists in balancing the branching versus extension of dendrites during neural development.ĭendrite development is largely governed by the modulation of intracellular pathways by extracellular signaling cues ( Dong et al., 2015). Our data suggest that these complexes affect dendrite development by differentially regulating the small-GTPase RhoA and actin-associated protein Cortactin. Whereas the delta:Pdlim5 complex enhances dendrite branching at the expense of elongation, the delta:Magi1 complex instead promotes lengthening. The phosphorylation state of this motif determines delta-catenin’s ability to bind either Pdlim5 or Magi1. In it, glutamate signaling activates mGluR5 receptors to promote Ckd5-mediated phosphorylation of the C-terminal PDZ-binding motif of delta-catenin. Here, we report a new mechanism instructing dendrites to branch versus extend. While several known processes shape the arbor, little is known of those that govern dendrite branching versus extension. It is thus vital that, during development, the dendritic arbor is adequately formed to enable proper neural circuit formation and function. In neurons, dendrites form the major sites of information receipt and integration.
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