Phase separation of an actin nucleator by junctional microtubules regulates epithelial function

Liquid-liquid phase separation (LLPS) is involved in various dynamic biological phenomena. In epithelial cells, dynamic regulation of junctional actin filaments tethered to the apical junctional complex (AJC) is critical for maintaining internal homeostasis against external perturbations; however, the role of LLPS in this process remains unknown. Here, after identifying a multifunctional actin nucleator, cordon bleu (Cobl), as an AJC-enriched microtubule-associated protein, we conducted comprehensive in vitro and in vivo analyses. We found that apical microtubules promoted LLPS of Cobl at the AJC, and Cobl actin assembly activity increased upon LLPS. Thus, microtubules spatiotemporally regulated junctional actin assembly for epithelial morphogenesis and paracellular barriers. Collectively, these findings established that LLPS of the actin nucleator Cobl mediated dynamic microtubule-actin cross-talk in junctions, which fine-tuned the epithelial barrier.

Automated summary

Liquid-liquid phase separation (LLPS) plays a role in dynamic biological phenomena. In this study, the role of LLPS in the dynamic regulation of junctional actin filaments in epithelial cells was investigated. The researchers identified a multifunctional actin nucleator called cordon bleu (Cobl) as an AJC-enriched microtubule-associated protein and conducted comprehensive in vitro and in vivo analyses. They found that apical microtubules promoted LLPS of Cobl at the AJC, leading to increased Cobl actin assembly activity and spatiotemporal regulation of junctional actin assembly for epithelial morphogenesis and paracellular barriers.