title: N-cadherin regulates spatially polarized signals through distinct p120ctn and β-catenin-dependent signalling pathways.
abstract: The spatial distribution of molecular signals within cells is crucial for cellular functions. Here, as a model to study the polarized spatial distribution of molecular activities, we used cells on micropatterned strips of fibronectin with one end free and the other end contacting a neighbouring cell. Phosphoinositide 3-kinase and the small GTPase Rac display greater activity at the free end, whereas myosin II light chain and actin filaments are enriched near the intercellular junction. Phosphoinositide 3-kinase and Rac polarization depend specifically on the N-cadherin-p120 catenin complex, whereas myosin II light chain and actin filament polarization depend on the N-cadherin-β-catenin complex. Integrins promote high phosphoinositide 3-kinase/Rac activities at the free end, and the N-cadherin-p120 catenin complex excludes integrin α5 at the junctions to suppress local phosphoinositide 3-kinase and Rac activity. We hence conclude that N-cadherin couples with distinct effectors to polarize phosphoinositide 3-kinase/Rac and myosin II light chain/actin filaments in migrating cells.
authors.affiliation: Department of Bioengineering, University of Illinois, Urbana-Champaign, Illinois 61801, USA.
authors.forename: Mingxing
authors.initials: M
authors.lastname: Ouyang
authors.forename: Shaoying
authors.initials: S
authors.lastname: Lu
authors.forename: Taejin
authors.initials: T
authors.lastname: Kim
authors.forename: Chin-En
authors.initials: CE
authors.lastname: Chen
authors.forename: Jihye
authors.initials: J
authors.lastname: Seong
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Leckband
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Albert B
authors.initials: AB
authors.lastname: Reynolds
authors.forename: Martin A
authors.initials: MA
authors.lastname: Schwartz
authors.forename: Yingxiao
authors.initials: Y
authors.lastname: Wang
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000378:metabolism*; D051177:Catenins / Q000378:metabolism*; D016764:Cell Polarity; D002645:Chickens; D006224:Cricetinae; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D007365:Intercellular Junctions / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism*; D020744:rac GTP-Binding Proteins; D000095002:Delta Catenin
chemical_list: D015820:Cadherins; D051177:Catenins; D005456:Fluorescent Dyes; D016023:Integrins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D051176:beta Catenin; D019869:Phosphatidylinositol 3-Kinases; D020744:rac GTP-Binding Proteins; D000095002:Delta Catenin