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

Yuji Mizotani, Mayu Suzuki, Kohji Hotta, Hidenori Watanabe, Kogiku Shiba, Kazuo Inaba, Etsu Tashiro, Kotaro Oka, Masaya Imoto

Research output: Contribution to journalArticle

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.

LanguageEnglish
PagesE8873-E8881
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number38
DOIs
Publication statusPublished - 2018 Sep 18

Fingerprint

Notochord
Growth
Larva
Myosin Type II
Pulsatile Flow
moesin
radixin
ezrin
Proteins

Keywords

  • 14-3-3
  • ERM
  • Myosin II
  • Pulsatile directed flow
  • Tubulogenesis

ASJC Scopus subject areas

  • General

Cite this

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.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, No. 38, 18.09.2018, p. E8873-E8881.

Research output: Contribution to journalArticle

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