AmotL2 links VE-cadherin to contractile actin fibres necessary for aortic lumen expansion.
Hultin SDepartment of Oncology and Pathology, Cancer Center Karolinska, Karolinska University Hospital, 171 76 Stockholm, Sweden.
Zheng YDepartment of Oncology and Pathology, Cancer Center Karolinska, Karolinska University Hospital, 171 76 Stockholm, Sweden.
Mojallal MDepartment of Oncology and Pathology, Cancer Center Karolinska, Karolinska University Hospital, 171 76 Stockholm, Sweden.
Vertuani SDepartment of Oncology and Pathology, Cancer Center Karolinska, Karolinska University Hospital, 171 76 Stockholm, Sweden.
Gentili CDepartment of Oncology and Pathology, Cancer Center Karolinska, Karolinska University Hospital, 171 76 Stockholm, Sweden.
Balland MLaboratoire interdisciplinaire de Physique, Université Joseph Fourier (Grenoble 1), Domaine Universitaire, Bat. E45 140, rue de la physique, Saint Martin d´Hères Cedex 9 38402 Grenoble, France.
Milloud RLaboratoire interdisciplinaire de Physique, Université Joseph Fourier (Grenoble 1), Domaine Universitaire, Bat. E45 140, rue de la physique, Saint Martin d´Hères Cedex 9 38402 Grenoble, France.
Helker CSBiological Faculty, University of Muenster, 48149 Muenster, Germany.
Adams RHMax Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany.
Herzog W1] Biological Faculty, University of Muenster, 48149 Muenster, Germany [2] Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany [3] Cluster of Excellence EXC 1003, Cells in Motion, CiM -, 48149 Münster, Germany.
Uhlen PDepartment of Medical Biochemistry and Biophysics, Karolinska Institute, 171 77 Stockholm, Sweden.
Majumdar A1] Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska University Hospital, 171 76 Stockholm, Sweden [2].
Holmgren L1] Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska University Hospital, 171 76 Stockholm, Sweden [2].
English
The assembly of individual endothelial cells into multicellular tubes is a complex morphogenetic event in vascular development. Extracellular matrix cues and cell-cell junctional communication are fundamental to tube formation. Together they determine the shape of endothelial cells and the tubular structures that they ultimately form. Little is known regarding how mechanical signals are transmitted between cells to control cell shape changes during morphogenesis. Here we provide evidence that the scaffold protein amotL2 is needed for aortic vessel lumen expansion. Using gene inactivation strategies in zebrafish, mouse and endothelial cell culture systems, we show that amotL2 associates to the VE-cadherin adhesion complex where it couples adherens junctions to contractile actin fibres. Inactivation of amotL2 dissociates VE-cadherin from cytoskeletal tensile forces that affect endothelial cell shape. We propose that the VE-cadherin/amotL2 complex is responsible for transmitting mechanical force between endothelial cells for the coordination of cellular morphogenesis consistent with aortic lumen expansion and function.