β1 Integrin Establishes Endothelial Cell Polarity and Arteriolar Lumen Formation via a Par3-Dependent Mechanism

Ann C. Zovein, Alfonso Luque, Kirsten A. Turlo, Jennifer J. Hofmann, Kathleen M. Yee, Michael S. Becker, Reinhard Fassler, Ira Mellman, Timothy F Lane, M. Luisa Iruela-Arispe*

*Corresponding author for this work

Research output: Contribution to journalArticle

174 Scopus citations

Abstract

Maintenance of single-layered endothelium, squamous endothelial cell shape, and formation of a patent vascular lumen all require defined endothelial cell polarity. Loss of β1 integrin (Itgb1) in nascent endothelium leads to disruption of arterial endothelial cell polarity and lumen formation. The loss of polarity is manifested as cuboidal-shaped endothelial cells with dysregulated levels and mislocalization of normally polarized cell-cell adhesion molecules, as well as decreased expression of the polarity gene Par3 (pard3). β1 integrin and Par3 are both localized to the endothelial layer, with preferential expression of Par3 in arterial endothelium. Luminal occlusion is also exclusively noted in arteries, and is partially rescued by replacement of Par3 protein in β1-deficient vessels. Combined, our findings demonstrate that β1 integrin functions upstream of Par3 as part of a molecular cascade required for endothelial cell polarity and lumen formation.

Original languageEnglish (US)
Pages (from-to)39-51
Number of pages13
JournalDevelopmental Cell
Volume18
Issue number1
DOIs
StatePublished - Jan 19 2010

Keywords

  • DEVBIO

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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    Zovein, A. C., Luque, A., Turlo, K. A., Hofmann, J. J., Yee, K. M., Becker, M. S., Fassler, R., Mellman, I., Lane, T. F., & Iruela-Arispe, M. L. (2010). β1 Integrin Establishes Endothelial Cell Polarity and Arteriolar Lumen Formation via a Par3-Dependent Mechanism. Developmental Cell, 18(1), 39-51. https://doi.org/10.1016/j.devcel.2009.12.006