Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX.
Program in Neuroscience, The University of Texas Graduate School of Biomedical Science, Houston, TX.
J Cell Biol. 2020 Nov 2;219(11). 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.
在神经元中，树突形成了信息接收和整合的主要部位。因此，在发育过程中，树突分支必须充分形成，以确保适当的神经回路形成和功能。虽然有几个已知的过程可以塑造树突，但对于控制树突分支与延伸的过程知之甚少。在这里，我们报告了一个新的机制，指导树突分支与延伸。在这个机制中，谷氨酸信号激活 mGluR5 受体，促进 Ckd5 介导的 δ-连环蛋白 C 端 PDZ 结合基序的磷酸化。该基序的磷酸化状态决定了 δ-连环蛋白结合 Pdlim5 或 Magi1 的能力。虽然 δ:Pdlim5 复合物以牺牲伸长为代价增强树突分支，但 δ:Magi1 复合物反而促进伸长。我们的数据表明，这些复合物通过差异调节小 GTPase RhoA 和肌动蛋白相关蛋白 Cortactin 来影响树突的发育。因此，我们揭示了 δ-连环蛋白内的一个“磷酸化开关”，受谷氨酸介导的信号通路的影响，有助于在神经发育过程中平衡树突的分支与延伸。
