Emergence of periodic circumferential actin cables from the anisotropic fusion of actin nanoclusters during tubulogenesis

Abstract The periodic circumferential cytoskeleton supports various tubular tissues1-5. Radial expansion of the tube lumen causes anisotropic tensile stress, which can be exploited as a geometric cue6. However, the molecular machinery linking anisotropy to robust circumferential patterning is poorly understood. Here, we aimed to reveal the emergent process of circumferential actin cable formation in a Drosophila tracheal tube7. During luminal expansion, sporadic actin nanoclusters emerge and exhibit circumferentially biased motion and fusion. RNAi screening revealed the formin family protein, DAAM, as an essential component of tensile stress sensing, and non-muscle myosin II as a component required for nanocluster fusion. A coarse-grained molecular dynamics simulation demonstrated that crosslinkers play a crucial role in nanocluster formation and cluster-to-cable transition occurs in response to mechanical anisotropy. Altogether, we propose that an actin nanocluster is an organizational unit that senses stress in the cortical membrane and builds a higher-order cable structure.