RT Journal Article
SR Electronic
T1 Dendrite branching receptor HPO-30 uses two novel mechanisms to regulate actin cytoskeletal remodeling
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.05.13.491788
DO 10.1101/2022.05.13.491788
A1 Daniel A. Kramer
A1 Heidy Y. Narvaez-Ortiz
A1 Rebecca Shi
A1 Kang Shen
A1 Julien Roche
A1 Brad J. Nolen
A1 Baoyu Chen
YR 2022
UL http://biorxiv.org/content/early/2022/06/28/2022.05.13.491788.abstract
AB Dendrite morphogenesis is essential to neural circuit formation, but the molecular mechanisms controlling the growth of complicated dendrite branches are not well understood. Prior studies using the highly branched C. elegans PVD sensory neuron identified a membrane co-receptor complex that transmits extracellular cues to intracellular actin remodeling machinery to promote high-order dendrite branching. In this complex, the transmembrane protein HPO-30 recruits the WAVE regulatory complex (WRC) from the cytosol 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 likely undergoes dimerization and induced folding to bind the WRC, with the binding simultaneously promoting WRC activation by the GTPase Rac1. Second, the dimerized HPO-30 ICD directly binds to both the sides and barbed end of actin filaments. The barbed end binding activity resembles that of the actin capping protein CapZ and prevents both actin polymerization and depolymerization. The novel dual functions of this dendrite receptor provide an intriguing model of how membrane proteins can use distinct mechanisms to fine-tune local actin dynamics.Competing Interest StatementThe authors have declared no competing interest.