The Rho-guanine nucleotide exchange factor Trio controls leukocyte transendothelial migration by promoting docking structure formation

Jos Van Rijssel, Jeffrey Kroon, Mark Hoogenboezem, Floris P.J. Van Alphen, Renske J. De Jong, Elena Kostadinova, Dirk Geerts, Peter L. Hordijk, Jaap D. Van Buul*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Leukocyte transendothelial migration involves the active participation of the endothelium through the formation of apical membrane protrusions that embrace adherent leukocytes, termed docking structures. Using live-cell imaging, we find that prior to transmigration, endothelial docking structures form around 80% of all neutrophils. Previously we showed that endothelial RhoG and SGEF control leukocyte transmigration. In this study, our data reveal that both full-length Trio and the first DH-PH (TrioD1) domain of Trio, which can activate Rac1 and RhoG, interact with ICAM-1 and are recruited to leukocyte adhesion sites. Moreover, upon clustering of ICAM-1, the Rho-guanine nucleotide exchange factor Trio activates Rac1, prior to activating RhoG, in a filamin-dependent manner. We further show that docking structure formation is initiated by ICAM-1 clustering into ring-like structures, which is followed by apical membrane protrusion. Interestingly, we find that Rac1 is required for ICAM-1 clustering, whereas RhoG controls membrane protrusion formation. Finally, silencing endothelial Trio expression or reducing TrioD1 activity without affecting SGEF impairs both docking structure formation and leukocyte transmigration. We conclude that Trio promotes leukocyte transendothelial migration by inducing endothelial docking structure formation in a filamin-dependent manner through the activation of Rac1 and RhoG.

Original languageEnglish
Pages (from-to)2831-2844
Number of pages14
JournalMolecular Biology of the Cell
Volume23
Issue number15
DOIs
Publication statusPublished - 1 Aug 2012

Cite this

Van Rijssel, J., Kroon, J., Hoogenboezem, M., Van Alphen, F. P. J., De Jong, R. J., Kostadinova, E., ... Van Buul, J. D. (2012). The Rho-guanine nucleotide exchange factor Trio controls leukocyte transendothelial migration by promoting docking structure formation. Molecular Biology of the Cell, 23(15), 2831-2844. https://doi.org/10.1091/mbc.E11-11-0907