Dendrite branching receptor HPO-30 uses two novel mechanisms to regulate actin cytoskeletal remodeling

Dendrite morphogenesis is essential to neural circuit formation, but the molecular mechanisms that control the growth of complicated dendrite branches are not well understood. Prior studies using the C. elegans PVD sensory neuron identified a multi-protein signaling complex that bridges extracellular cues with intracellular actin remodeling to promote high-order dendrite branching. In this complex, the transmembrane protein HPO-30 recruits the WAVE Regulatory Complex (WRC) to dendrite branching sites, where WRC stimulates the Arp2/3 complex to polymerize actin. Here we report biochemical and structural characterization of this interaction, revealing that the intracellular domain (ICD) of HPO-30 uses two novel mechanisms to regulate the actin cytoskeleton. First, the unstructured HPO-30 ICD undergoes dimerization and folding into a three-dimensional structure in order to bind the WRC. Second, the HPO-30 ICD directly binds to actin filaments, which stabilizes actin structures by preventing both actin polymerization and depolymerization. The novel dual functions of this dendrite receptor provide an intriguing example of how membrane proteins can use different mechanisms to locally fine-tune actin dynamics. ### Competing Interest Statement The authors have declared no competing interest.