A Dendritic Guidance Receptor Complex Brings Together Distinct Actin Regulators to Drive Efficient F-Actin Assembly and Branching

Publication date: 7 May 2018
Source:Developmental Cell, Volume 45, Issue 3
Author(s): Wei Zou, Xintong Dong, Timothy R. Broederdorf, Ao Shen, Daniel A. Kramer, Rebecca Shi, Xing Liang, David M. Miller, Yang K. Xiang, Ryohei Yasuda, Baoyu Chen, Kang Shen
Proper morphogenesis of dendrites plays a fundamental role in the establishment of neural circuits. The molecular mechanism by which dendrites grow highly complex branches is not well understood. Here, using the Caenorhabditis elegans PVD neuron, we demonstrate that high-order dendritic branching requires actin polymerization driven by coordinated interactions between two membrane proteins, DMA-1 and HPO-30, with their cytoplasmic interactors, the RacGEF TIAM-1 and the actin nucleation promotion factor WAVE regulatory complex (WRC). The dendrite branching receptor DMA-1 directly binds to the PDZ domain of TIAM-1, while the claudin-like protein HPO-30 directly interacts with the WRC. On dendrites, DMA-1 and HPO-30 form a receptor-associated signaling complex to bring TIAM-1 and the WRC to close proximity, leading to elevated assembly of F-actin needed to drive high-order dendrite branching. The synergistic activation of F-actin assembly by scaffolding distinct actin regulators might represent a general mechanism in promoting complex dendrite arborization.

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Teaser

Zou et al. uncover a molecular mechanism for complex dendrite formation. The dendrite guidance receptor DMA-1 interacts with the claudin-like protein HPO-30 to scaffold two actin regulators, the RacGEF TIAM-1 and the WAVE regulatory complex. The spatial proximity of these factors promotes efficient actin polymerization and drives high-order dendritic branching.


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