14-3-3εa directs the pulsatile transport of basal factors toward the apical domain for lumen growth in tubulogenesis

• Mizotani, Yuji

• Suzuki, Mayu

• Hotta, Kohji

• Watanabe, Hidenori

• SHIBA, Kogiku

• INABA, Kazuo

• Tashiro, Etsu

• Oka, Kotaro

• Imoto, Masaya

Abstract

The Ciona notochord has emerged as a simple and tractable in vivo model for tubulogenesis. Here, using a chemical genetics approach, we identified UTKO1 as a selective small molecule inhibitor of notochord tubulogenesis. We identified 14-3-3εa protein as a direct binding partner of UTKO1 and showed that 14-3-3εa knockdown leads to failure of notochord tubulogenesis. We found that UTKO1 prevents 14-3-3εa from interacting with ezrin/radixin/moesin (ERM), which is required for notochord tubulogenesis, suggesting that interactions between 14-3-3εa and ERM play a key role in regulating the early steps of tubulogenesis. Using live imaging, we found that, as lumens begin to open between neighboring cells, 14-3-3εa and ERM are highly colocalized at the basal cortex where they undergo cycles of accumulation and disappearance. Interestingly, the disappearance of 14-3-3εa and ERM during each cycle is tightly correlated with a transient flow of 14-3-3εa, ERM, myosin II, and other cytoplasmic elements from the basal surface toward the lumen-facing apical domain, which is often accompanied by visible changes in lumen architecture. Both pulsatile flow and lumen formation are abolished in larvae treated with UTKO1, in larvae depleted of either 14-3-3εa or ERM, or in larvae expressing a truncated form of 14-3-3εa that lacks the ability to interact with ERM. These results suggest that 14-3-3εa and ERM interact at the basal cortex to direct pulsatile basal accumulation and basal–apical transport of factors that are essential for lumen formation. We propose that similar mechanisms may underlie or may contribute to lumen formation in tubulogenesis in other systems.

Journal

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 115 (38), E8873-E8881, 2018-08

  National Academy of Sciences

Keywords

• Multidisciplinary

Details

• CRID: 1050282677532576768
• NII Article ID: 120007133686
• NII Book ID: AA00786025
• DOI: 10.1073/pnas.1808756115
• ISSN: 10916490
• ISSN: 00278424
• HANDLE: 2241/00154020
• Web Site: https://tsukuba.repo.nii.ac.jp/records/48532
• Web Site: http://www.pnas.org/syndication/doi/10.1073/pnas.1808756115
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.1808756115
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN