Novel phospho-switch function of delta-catenin in dendrite development

• Published in: The Journal of cell biology Vol. 219; no. 11; p. 1
• Main Authors: Baumert, Ryan, Ji, Hong, Paulucci-Holthauzen, Adriana, Wolfe, Aaron, Sagum, Cari, Hodgson, Louis, Arikkath, Jyothi, Chen, Xiaojiang, Bedford, Mark T, Waxham, M Neal, McCrea, Pierre D
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 02.11.2020
• Subjects: Actin; Animals; Catenin; Catenins - genetics; Catenins - metabolism; Cell Signaling; Circuits; Dendrites; Dendrites - physiology; Dendritic branching; Dendritic structure; Development; Elongation; Glutamic acid receptors (metabotropic); Guanylate Kinases - genetics; Guanylate Kinases - metabolism; HEK293 Cells; Hippocampus - cytology; Hippocampus - metabolism; Humans; LIM Domain Proteins - genetics; LIM Domain Proteins - metabolism; Neurogenesis; Neurons - cytology; Neurons - metabolism; Neuroscience; Phosphorylation; Rats; rhoA GTP-Binding Protein - genetics; rhoA GTP-Binding Protein - metabolism; RhoA protein; Signal transduction; Signaling
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201909166

In neurons, dendrites form the major sites of information receipt and integration. It is thus vital that, during development, the dendritic arbor is adequately formed to enable proper neural circuit formation and function. While several known processes shape the arbor, little is known of those that govern dendrite branching versus extension. Here, we report a new mechanism instructing dendrites to branch versus extend. In it, glutamate signaling activates mGluR5 receptors to promote Ckd5-mediated phosphorylation of the C-terminal PDZ-binding motif of delta-catenin. The phosphorylation state of this motif determines delta-catenin's ability to bind either Pdlim5 or Magi1. Whereas the delta:Pdlim5 complex enhances dendrite branching at the expense of elongation, the delta:Magi1 complex instead promotes lengthening. Our data suggest that these complexes affect dendrite development by differentially regulating the small-GTPase RhoA and actin-associated protein Cortactin. 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.