マツイ　タケシ   Takeshi Matsui   松井　毅    所属   応用生物学部 応用生物学科    職種   教授
言語種別	英語
発行・発表の年月	2013/11
形態種別	学術論文
査読	査読あり
標題	The association of microtubules with tight junctions is promoted by cingulin phosphorylation by AMPK
執筆形態	共著
掲載誌名	Journal of Cell Biology
掲載区分	国外
巻・号・頁	203(4),pp.605-614
総ページ数	10
著者・共著者	Tomoki Yano, Takeshi Matsui, Atsushi Tamura, Masami Uji, Sachiko Tsukita
概要	Epithelial cells characteristically have noncentrosomal microtubules that are arranged in the apicobasal direction. In this paper, we examined cell sheets formed by an epithelial (Eph4) cell line by structure illumination microscopy and found a previously not clearly described planar apical network of noncentrosomal microtubules (MTs) in which the sides of the MT bundles were associated with tight junctions (TJs). In a gel overlay assay with taxol-stabilized MTs, cingulin showed strong binding to MTs, and a domain analysis showed that this binding occurred through cingulin’s N-terminal region. The association of planar apical MTs with TJs was compromised by cingulin knockdown (KD) or the expression of dephosphomimetic mutants of cingulin at its adenosine monophosphate–activated protein kinase (AMPK) target sites, whereas phosphorylation at these sites facilitated cingulin–tubulin binding. In addition, although wild-type colonies formed spheres in 3D culture, the cingulin KD cells had anisotropic shapes. These findings collectively suggest that the regulated cingulin–MT association has a specific role in TJ-related epithelial morphogenesis that is sensitive to metabolic homeostasis-related AMPK activity.