title: AmotL2 links VE-cadherin to contractile actin fibres necessary for aortic lumen expansion.
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.
authors.affiliation: Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska University Hospital, 171 76 Stockholm, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Hultin
authors.affiliation: Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska University Hospital, 171 76 Stockholm, Sweden.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska University Hospital, 171 76 Stockholm, Sweden.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Mojallal
authors.affiliation: Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska University Hospital, 171 76 Stockholm, Sweden.
authors.forename: Simona
authors.initials: S
authors.lastname: Vertuani
authors.affiliation: Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska University Hospital, 171 76 Stockholm, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Gentili
authors.affiliation: 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.
authors.forename: Martial
authors.initials: M
authors.lastname: Balland
authors.affiliation: 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.
authors.forename: Rachel
authors.initials: R
authors.lastname: Milloud
authors.affiliation: Abt. Zellbiologie, Biozentrum/Uni Basel, Klingelbergstrasse 70, CH 4056 Basel, Switzerland.
authors.forename: Heinz-Georg
authors.initials: HG
authors.lastname: Belting
authors.affiliation: Abt. Zellbiologie, Biozentrum/Uni Basel, Klingelbergstrasse 70, CH 4056 Basel, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Affolter
authors.affiliation: Biological Faculty, University of Muenster, 48149 Muenster, Germany.
authors.forename: Christian S M
authors.initials: CS
authors.lastname: Helker
authors.affiliation: Max Planck Institute for Molecular Biomedicine, 48149 Muenster, Germany.
authors.forename: Ralf H
authors.initials: RH
authors.lastname: Adams
authors.affiliation: 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.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Herzog
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institute, 171 77 Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Uhlen
authors.affiliation: 1] Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska University Hospital, 171 76 Stockholm, Sweden [2].
authors.forename: Arindam
authors.initials: A
authors.lastname: Majumdar
authors.affiliation: 1] Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska University Hospital, 171 76 Stockholm, Sweden [2].
authors.forename: Lars
authors.initials: L
authors.lastname: Holmgren
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D022005:Adherens Junctions / Q000378:metabolism; D000091082:Angiomotins; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001011:Aorta / Q000166:cytology / Q000254:growth & development*; D015820:Cadherins / Q000378:metabolism*; D002450:Cell Communication; D048430:Cell Shape; D003285:Contractile Proteins / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000254:growth & development / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D055785:Gene Knockdown Techniques; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis; D060172:Morpholinos / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*; D000099152:Cadherin 5
chemical_list: D000091082:Angiomotins; D015703:Antigens, CD; D015820:Cadherins; D003285:Contractile Proteins; D008565:Membrane Proteins; D060172:Morpholinos; D034741:RNA, Small Interfering; D029961:Zebrafish Proteins; D000099152:Cadherin 5; C519597:amotl2a protein, zebrafish