A microtubule-LUZP1 association around tight junction promotes epithelial cell apical constriction

EMBO J. 2021 Jan 15;40(2):e104712. doi: 10.15252/embj.2020104712. Epub 2020 Dec 21.


Apical constriction is critical for epithelial morphogenesis, including neural tube formation. Vertebrate apical constriction is induced by di-phosphorylated myosin light chain (ppMLC)-driven contraction of actomyosin-based circumferential rings (CRs), also known as perijunctional actomyosin rings, around apical junctional complexes (AJCs), mainly consisting of tight junctions (TJs) and adherens junctions (AJs). Here, we revealed a ppMLC-triggered system at TJ-associated CRs for vertebrate apical constriction involving microtubules, LUZP1, and myosin phosphatase. We first identified LUZP1 via unbiased screening of microtubule-associated proteins in the AJC-enriched fraction. In cultured epithelial cells, LUZP1 was found localized at TJ-, but not at AJ-, associated CRs, and LUZP1 knockout resulted in apical constriction defects with a significant reduction in ppMLC levels within CRs. A series of assays revealed that ppMLC promotes the recruitment of LUZP1 to TJ-associated CRs, where LUZP1 spatiotemporally inhibits myosin phosphatase in a microtubule-facilitated manner. Our results uncovered a hitherto unknown microtubule-LUZP1 association at TJ-associated CRs that inhibits myosin phosphatase, contributing significantly to the understanding of vertebrate apical constriction.

Keywords: LUZP1; actomyosin-based circumferential rings; apical constriction; apical microtubules; tight junction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins / metabolism
  • Adherens Junctions / metabolism
  • Animals
  • Cell Line
  • Chickens
  • DNA-Binding Proteins / metabolism*
  • Epithelial Cells / metabolism*
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Microtubules / metabolism*
  • Myosins / metabolism
  • Sf9 Cells
  • Tight Junctions / metabolism*


  • Actins
  • DNA-Binding Proteins
  • Luzp1 protein, mouse
  • Myosins