Matsuzawa Kenji, Ohga Hayato, Shigetomi Kenta, Shiiya Tomohiro, Hirashima Masanori, Ikenouchi Junichi
Department of Biology, Faculty of Sciences, Kyushu University, 774 Motooka, Nishi-ku, Fukuoka, 819-0395, Japan.
Division of Pharmacology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan.
Commun Biol. 2021 Mar 12;4(1):337. doi: 10.1038/s42003-021-01874-z.
Constriction of the apical plasma membrane is a hallmark of epithelial cells that underlies cell shape changes in tissue morphogenesis and maintenance of tissue integrity in homeostasis. Contractile force is exerted by a cortical actomyosin network that is anchored to the plasma membrane by the apical junctional complexes (AJC). In this study, we present evidence that MAGI proteins, structural components of AJC whose function remained unclear, regulate apical constriction of epithelial cells through the Par polarity proteins. We reveal that MAGIs are required to uniformly distribute Partitioning defective-3 (Par-3) at AJC of cells throughout the epithelial monolayer. MAGIs recruit ankyrin-repeat-, SH3-domain- and proline-rich-region-containing protein 2 (ASPP2) to AJC, which modulates Par-3-aPKC to antagonize ROCK-driven contractility. By coupling the adhesion machinery to the polarity proteins to regulate cellular contractility, we propose that MAGIs play essential and central roles in maintaining steady state intercellular tension throughout the epithelial cell sheet.
顶端质膜的收缩是上皮细胞的一个标志，它是组织形态发生过程中细胞形状变化以及内环境稳态下组织完整性维持的基础。收缩力由皮质肌动球蛋白网络施加，该网络通过顶端连接复合体（AJC）锚定在质膜上。在本研究中，我们提供证据表明，AJC的结构成分MAGI蛋白（其功能尚不清楚）通过Par极性蛋白调节上皮细胞的顶端收缩。我们发现，MAGI蛋白对于在上皮单层细胞的AJC处均匀分布Par-3是必需的。MAGI蛋白将含锚蛋白重复序列、SH3结构域和富含脯氨酸区域的蛋白2（ASPP2）招募至AJC，后者调节Par-3-aPKC以拮抗ROCK驱动的收缩性。通过将黏附机制与极性蛋白偶联以调节细胞收缩性，我们提出MAGI蛋白在维持整个上皮细胞片层的稳态细胞间张力方面发挥着至关重要的核心作用。
