title: An EMMPRIN-γ-catenin-Nm23 complex drives ATP production and actomyosin contractility at endothelial junctions.
abstract: Cell-cell adhesions are important sites through which cells experience and resist forces. In endothelial cells, these forces regulate junction dynamics and determine endothelial barrier strength. We identify the Ig superfamily member EMMPRIN (also known as basigin) as a coordinator of forces at endothelial junctions. EMMPRIN localization at junctions correlates with endothelial junction strength in different mouse vascular beds. Accordingly, EMMPRIN-deficient mice show altered junctions and increased junction permeability. Lack of EMMPRIN alters the localization and function of VE-cadherin (also known as cadherin-5) by decreasing both actomyosin contractility and tugging forces at endothelial cell junctions. EMMPRIN ensures proper actomyosin-driven maturation of competent endothelial junctions by forming a molecular complex with γ-catenin (also known as junction plakoglobin) and Nm23 (also known as NME1), a nucleoside diphosphate kinase, thereby locally providing ATP to fuel the actomyosin machinery. These results provide a novel mechanism for the regulation of actomyosin contractility at endothelial junctions and might have broader implications in biological contexts such as angiogenesis, collective migration and tissue morphogenesis by coupling compartmentalized energy production to junction assembly.
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Moreno
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Gonzalo
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Gómez-Escudero
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
authors.forename: Ángela
authors.initials: Á
authors.lastname: Pollán
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Acín-Pérez
authors.affiliation: University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Breckenridge
authors.affiliation: Instituto de Investigación Sanitaria Princesa. Universidad Autónoma de Madrid, 28006 Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Yáñez-Mó
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Barreiro
authors.affiliation: FIRC Institute of Molecular Oncology, University of Milan, 20139 Milan, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Orsenigo
authors.affiliation: Nagoya University, Nagoya, 464-8601, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kadomatsu
authors.affiliation: University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Enríquez
authors.affiliation: FIRC Institute of Molecular Oncology, University of Milan, 20139 Milan, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Dejana
authors.affiliation: Instituto de Investigación Sanitaria Princesa. Universidad Autónoma de Madrid, 28006 Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain agarroyo@cnic.es.
authors.forename: Alicia G
authors.initials: AG
authors.lastname: Arroyo
mesh_terms: D000205:Actomyosin / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D051926:Basigin / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D042783:Endothelial Cells / Q000166:cytology*; D004730:Endothelium, Vascular / Q000378:metabolism; D007365:Intercellular Junctions / Q000378:metabolism; D051379:Mice; D054778:NM23 Nucleoside Diphosphate Kinases / Q000378:metabolism*; D051185:gamma Catenin / Q000378:metabolism*
chemical_list: C497887:Bsg protein, mouse; D003598:Cytoskeletal Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D051185:gamma Catenin; D051926:Basigin; D000255:Adenosine Triphosphate; D000205:Actomyosin; C517939:Nme1 protein, mouse
keywords: ATP; Actomyosin contractility; EMMPRIN; Endothelial junctions; NDPK; Nm23; Nucleoside diphosphate kinase; Vascular integrity; γ-catenin