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A microtubule‐LUZP1 association around tight junction promotes epithelial cell apical constriction
Author(s) -
Yano Tomoki,
Tsukita Kazuto,
Kanoh Hatsuho,
Nakayama Shogo,
Kashihara Hiroka,
Mizuno Tomoaki,
Tanaka Hiroo,
Matsui Takeshi,
Goto Yuhei,
Komatsubara Akira,
Aoki Kazuhiro,
Takahashi Ryosuke,
Tamura Atsushi,
Tsukita Sachiko
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2020104712
Subject(s) - biology , tight junction , microtubule , microbiology and biotechnology , constriction , apical constriction , epithelium , cell junction , association (psychology) , cell , genetics , morphogenesis , gene , endocrinology , philosophy , epistemology
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.