Willin and Par3 cooperatively regulate epithelial apical constriction through a PKC-mediated ROCK phosphorylation

被引:94
作者
Ishiuchi, Takashi [1 ,2 ]
Takeichi, Masatoshi [1 ]
机构
[1] RIKEN Ctr Dev Biol, Chuo Ku, Kobe, Hyogo 6500047, Japan
[2] Kyoto Univ, Grad Sch Biostudies, Sakyo Ku, Kyoto 6068502, Japan
关键词
PROTEIN-KINASE-C; CELL-POLARITY; TIGHT JUNCTION; DOMAIN SIZE; DROSOPHILA; PATHWAY; SHAPE; ADHESION; BAZOOKA; COMPLEX;
D O I
10.1038/ncb2274
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Apical-domain constriction is important for regulating epithelial morphogenesis. Epithelial cells are connected by apical junctional complexes (AJCs) that are lined with circumferential actomyosin cables. The contractility of the secables is regulated by Rho-associated kinases (ROCKs). Here, we report that Willin (a FERM-domain protein) and Par3 (a polarity-regulating protein) cooperatively regulate ROCK-dependent apical constriction. We found that Willin recruits aPKC and Par6 to the AJCs, independently of Par3. Simultaneous depletion of Willin and Par3 completely removed aPKC and Par6 from the AJCs and induced apical constriction. Induced constriction was through upregulation of the level of AJC-associated ROCKs, which was due to loss of aPKC. Our results indicate that aPKC phosphorylates ROCK and suppresses its junctional localization, there by allowing cells to retain normally shaped apical domains. Thus, we have uncovered a Willin/Par3-aPKC-ROCK pathway that controls epithelial apical morphology.
引用
收藏
页码:860 / U297
页数:18
相关论文
共 35 条
[1]  
Amano M, 2000, METHOD ENZYMOL, V325, P149
[2]   Myosin-dependent junction remodelling controls planar cell intercalation and axis elongation [J].
Bertet, C ;
Sulak, L ;
Lecuit, T .
NATURE, 2004, 429 (6992) :667-671
[3]   Multicellular rosette formation links planar cell polarity to tissue morphogenesis [J].
Blankenship, J. Todd ;
Backovic, Stephanie T. ;
Sanny, Justina S. P. ;
Weitz, Ori ;
Zallen, Jennifer A. .
DEVELOPMENTAL CELL, 2006, 11 (04) :459-470
[4]   Par-3 controls tight junction assembly through the Rac exchange factor Tiam1 [J].
Chen, XY ;
Macara, IG .
NATURE CELL BIOLOGY, 2005, 7 (03) :262-U72
[5]   The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM) [J].
Ebnet, K ;
Suzuki, A ;
Horikoshi, Y ;
Hirose, T ;
Meyer zu Brickwedde, MK ;
Ohno, S ;
Vestweber, D .
EMBO JOURNAL, 2001, 20 (14) :3738-3748
[6]   The Hippo pathway regulates apical-domain size independently of its growth-control function [J].
Genevet, Alice ;
Polesello, Cedric ;
Blight, Ken ;
Robertson, Francesca ;
Collinson, Lucy M. ;
Pichaud, Franck ;
Tapon, Nicolas .
JOURNAL OF CELL SCIENCE, 2009, 122 (14) :2360-2370
[7]   Cdc42, Par6, and aPKC Regulate Arp2/3-Mediated Endocytosis to Control Local Adherens Junction Stability [J].
Georgiou, Marios ;
Marinari, Eliana ;
Burden, Jemima ;
Baum, Buzz .
CURRENT BIOLOGY, 2008, 18 (21) :1631-1638
[8]   A novel 4.1 ezrin radixin moesin (FERM)-containing protein, 'Willin' [J].
Gunn-Moore, FJ ;
Welsh, GI ;
Herron, LR ;
Brannigan, F ;
Venkateswarlu, K ;
Gillespie, S ;
Brandwein-Gensler, M ;
Madan, R ;
Tavaré, JM ;
Brophy, PJ ;
Prystowsky, MB ;
Guild, S .
FEBS LETTERS, 2005, 579 (22) :5089-5094
[9]   The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis [J].
Hamaratoglu, F ;
Willecke, M ;
Kango-Singh, M ;
Nolo, R ;
Hyun, E ;
Tao, CY ;
Jafar-Nejad, H ;
Halder, G .
NATURE CELL BIOLOGY, 2006, 8 (01) :27-U9
[10]   The Hippo tumor-suppressor pathway regulates apical-domain size in parallel to tissue growth [J].
Hamaratoglu, Fisun ;
Gajewski, Kathleen ;
Sansores-Garcia, Leticia ;
Morrison, Clayton ;
Tao, Chunyao ;
Halder, Georg .
JOURNAL OF CELL SCIENCE, 2009, 122 (14) :2351-2359