2. Academic Validation
  3. AmotL2 links VE-cadherin to contractile actin fibres necessary for aortic lumen expansion

AmotL2 links VE-cadherin to contractile actin fibres necessary for aortic lumen expansion

  • Nat Commun. 2014 May 7:5:3743. doi: 10.1038/ncomms4743.
Sara Hultin 1,  Yujuan Zheng 1,  Mahdi Mojallal 1,  Simona Vertuani 1,  Christian Gentili 1,  Martial Balland 2,  Rachel Milloud 2,  Heinz-Georg Belting 3,  Markus Affolter 3,  Christian S M Helker 4,  Ralf H Adams 5,  Wiebke Herzog 6,  Per Uhlen 7,  Arindam Majumdar 8,  Lars Holmgren 8
Affiliations

Affiliations

  • 1 Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska University Hospital, 171 76 Stockholm, Sweden.
  • 2 Laboratoire 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.
  • 3 Abt. Zellbiologie, Biozentrum/Uni Basel, Klingelbergstrasse 70, CH 4056 Basel, Switzerland.
  • 4 Biological Faculty, University of Muenster, 48149 Muenster, Germany.
  • 5 Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany.
  • 6 1] 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.
  • 7 Department of Medical Biochemistry and Biophysics, Karolinska Institute, 171 77 Stockholm, Sweden.
  • 8 1] Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska University Hospital, 171 76 Stockholm, Sweden [2].
PMID: 24806444 DOI: 10.1038/ncomms4743
Abstract

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.

Figures