title: VE-cadherin interacts with cell polarity protein Pals1 to regulate vascular lumen formation.
abstract: Blood vessel tubulogenesis requires the formation of stable cell-to-cell contacts and the establishment of apicobasal polarity of vascular endothelial cells. Cell polarity is regulated by highly conserved cell polarity protein complexes such as the Par3-aPKC-Par6 complex and the CRB3-Pals1-PATJ complex, which are expressed by many different cell types and regulate various aspects of cell polarity. Here we describe a functional interaction of VE-cadherin with the cell polarity protein Pals1. Pals1 directly interacts with VE-cadherin through a membrane-proximal motif in the cytoplasmic domain of VE-cadherin. VE-cadherin clusters Pals1 at cell-cell junctions. Mutating the Pals1-binding motif in VE-cadherin abrogates the ability of VE-cadherin to regulate apicobasal polarity and vascular lumen formation. In a similar way, deletion of the Par3-binding motif at the C-terminus of VE-cadherin impairs apicobasal polarity and vascular lumen formation. Our findings indicate that the biological activity of VE-cadherin in regulating endothelial polarity and vascular lumen formation is mediated through its interaction with the two cell polarity proteins Pals1 and Par3.
authors.affiliation: Institute-Associated Research Group "Cell Adhesion and Cell Polarity,", University of Münster, 48419 Münster, Germany Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Münster, 48419 Münster, Germany Interdisciplinary Clinical Research Center, University of Münster, 48419 Münster, Germany.
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Brinkmann
authors.affiliation: Institute-Associated Research Group "Cell Adhesion and Cell Polarity,", University of Münster, 48419 Münster, Germany Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Münster, 48419 Münster, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Steinbacher
authors.affiliation: Institute-Associated Research Group "Cell Adhesion and Cell Polarity,", University of Münster, 48419 Münster, Germany Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Münster, 48419 Münster, Germany Interdisciplinary Clinical Research Center, University of Münster, 48419 Münster, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hartmann
authors.affiliation: Institute-Associated Research Group "Cell Adhesion and Cell Polarity,", University of Münster, 48419 Münster, Germany Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Münster, 48419 Münster, Germany Interdisciplinary Clinical Research Center, University of Münster, 48419 Münster, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kummer
authors.affiliation: Institute-Associated Research Group "Cell Adhesion and Cell Polarity,", University of Münster, 48419 Münster, Germany Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Münster, 48419 Münster, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Pajonczyk
authors.affiliation: Laboratory for Cell Polarity and Organogenesis, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Mirzapourshafiyi
authors.affiliation: Laboratory for Cell Polarity and Organogenesis, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakayama
authors.affiliation: Department of Internal Medicine D, Division of Molecular Nephrology, University Hospital Münster, Albert-Schweitzer-Campus 1, University of Münster, 48419 Münster, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Weide
authors.affiliation: Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Münster, 48419 Münster, Germany Cells-in-Motion Cluster of Excellence (EXC 1003-CiM), University of Münster, 48419 Münster, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Gerke
authors.affiliation: Institute-Associated Research Group "Cell Adhesion and Cell Polarity,", University of Münster, 48419 Münster, Germany Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Münster, 48419 Münster, Germany Interdisciplinary Clinical Research Center, University of Münster, 48419 Münster, Germany ebnetk@uni-muenster.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Ebnet
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D001665:Binding Sites; D015820:Cadherins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D016764:Cell Polarity / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D009703:Nucleoside-Phosphate Kinase / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D011485:Protein Binding; D019108:Tight Junctions / Q000378:metabolism; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D008565:Membrane Proteins; D009703:Nucleoside-Phosphate Kinase; D000099152:Cadherin 5; C501307:MPP5 protein, human