Vav3-induced cytoskeletal dynamics contribute to heterotypic properties of endothelial barriers

Georg Hilfenhaus, Dai Phuong Nguyen, Jonathan Freshman, Divya Prajapati, Feiyang Ma, Dana Song, Safiyyah Ziyad, Myriam Cuadrado, Matteo Pellegrini, Xosé R. Bustelo, M. Luisa Iruela‑Arispe*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Through multiple cell-cell and cell-matrix interactions, epithelial and endothelial sheets form tight barriers. Modulators of the cytoskeleton contribute to barrier stability and act as rheostats of vascular permeability. In this study, we sought to identify cytoskeletal regulators that underlie barrier diversity across vessels. To achieve this, we correlated functional and structural barrier features to gene expression of endothelial cells (ECs) derived from different vascular beds. Within a subset of identified candidates, we found that the guanosine nucleotide exchange factor Vav3 was exclusively expressed by microvascular ECs and was closely associated with a high-resistance barrier phenotype. Ectopic expression of Vav3 in large artery and brain ECs significantly enhanced barrier resistance and cortical rearrangement of the actin cytoskeleton. Mechanistically, we found that the barrier effect of Vav3 is dependent on its Dbl homology domain and downstream activation of Rap1. Importantly, inactivation of Vav3 in vivo resulted in increased vascular leakage, highlighting its function as a key regulator of barrier stability.

Original languageEnglish (US)
Pages (from-to)2813-2830
Number of pages18
JournalJournal of Cell Biology
Issue number8
StatePublished - Aug 1 2018

ASJC Scopus subject areas

  • Cell Biology

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