Endothelial basement membrane laminin 511 is essential for shear stress response

Research output: Contribution to journalArticle

Abstract

Shear detection and mechanotransduction by arterial endothelium requires junctional complexes containing PECAM-1 and VE-cadherin, as well as firm anchorage to the underlying basement membrane. While considerable information is available for junctional complexes in these processes, gained largely from in vitro studies, little is known about the contribution of the endothelial basement membrane. Using resistance artery explants, we show that the integral endothelial basement membrane component, laminin 511 (laminin α5), is central to shear detection and mechanotransduction and its elimination at this site results in ablation of dilation in response to increased shear stress. Loss of endothelial laminin 511 correlates with reduced cortical stiffness of arterial endothelium in vivo, smaller integrin β1-positive/vinculin-positive focal adhesions, and reduced junctional association of actin–myosin II. In vitro assays reveal that β1 integrin-mediated interaction with laminin 511 results in high strengths of adhesion, which promotes p120 catenin association with VE-cadherin, stabilizing it at cell junctions and increasing cell–cell adhesion strength. This highlights the importance of endothelial laminin 511 in shear response in the physiologically relevant context of resistance arteries.

Details

Authors
  • Jacopo Di Russo
  • Anna Liisa Luik
  • Lema Yousif
  • Sigmund Budny
  • Hans Oberleithner
  • Verena Hofschröer
  • Juergen Klingauf
  • Ed van Bavel
  • Erik N T P Bakker
  • Per Hellstrand
  • Anirban Bhattachariya
  • Sebastian Albinsson
  • Frederic Pincet
  • Rupert Hallmann
  • Lydia M. Sorokin
Organisations
External organisations
  • University of Münster
  • University of Amsterdam
  • École Normale Supérieure
  • Pierre and Marie Curie University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology

Keywords

  • endothelial cells, focal adhesions, laminin 511, shear stress, VE-cadherin
Original languageEnglish
Pages (from-to)183-201
Number of pages19
JournalEMBO Journal
Volume36
Issue number2
StatePublished - 2017 Jan 17
Peer-reviewedYes