Kazuto Tsukita, Manabu Kitamata, Hiroka Kashihara, Tomoki Yano, Ikuko Fujiwara, Timothy F Day, Tatsuya Katsuno, Jaewon Kim, Fumiko Takenaga, Hiroo Tanaka, Sungsu Park, Makoto Miyata, Hitomi Watanabe, Gen Kondoh, Ryosuke Takahashi, Atsushi Tamura, Sachiko Tsukita (2023) Phase separation of an actin nucleator by junctional microtubules regulates epithelial function., Science advances, Volume 9, Number 7, pp. eadf6358
Published in 2023 Feb 15 (Electronic publication in Feb. 15, 2023, midnight )
(Abstract) 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.(MeSH Terms)