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

Abstract

Summary 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 C. 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, and 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.

Stress-induced dendritic branching inC. elegansrequires both common arborization effectors and stress-responsive molecular pathways

“…In the PVDs, DMA-1 acts through a protein complex for proper branching (10,11,17,18). sax-7 encodes a cell adhesion molecule, homologous to mammalian L1CAM, which acts in the surrounding hypodermis to control PVD arborization (9,10).…”

Claudins in the brain: Unconventional functions in neurons

“…First, In polymodal nociceptive for mechanosensation and thermosensation (PVD) neurons, higher order dendritic branching is maintained by the claudin HPO-30, which directly interacts with the Wave regulatory complex (WRC). 26 Second, we have shown that a claudin-like protein, HIC-1 interacts with an actin-binding protein, NAB-1/Neurabin through its PDZ binding motif in C. elegans cholinergic synapses. 27 These studies suggest that claudins function at dendrites and synapses similar to how they function at the epithelium.…”

“…Very recently, two studies in Caenorhabditis elegans have shown that claudin‐like proteins interact with actin/actin binding proteins at synapses/dendrites. First, In polymodal nociceptive for mechanosensation and thermosensation (PVD) neurons, higher order dendritic branching is maintained by the claudin HPO‐30, which directly interacts with the Wave regulatory complex (WRC) . Second, we have shown that a claudin‐like protein, HIC‐1 interacts with an actin‐binding protein, NAB‐1/Neurabin through its PDZ binding motif in C. elegans cholinergic synapses .…”

“…They go on to propose that the association between DMA‐1 and HPO‐30 recruits both TIAM‐1 and WRC to the dendritic membranes. This signaling complex is required for the localization and dynamics of the actin cytoskeleton, which ultimately controls the highly branched dendritic arbors in PVD neurons (Figure A and Reference ).…”

“…A, HPO‐30 interaction with DMA‐1 receptor regulates actin cytoskeleton and dentritic branching in C. elegans PVD neurons. This image is adapted with modifications from Reference . B, HPO‐30 regulates LAChRs at the C. elegans neuromuscular junction.…”