title: Rho GEFs in endothelial junctions: Effector selectivity and signaling integration determine junctional response.
abstract: Rho GTPases are cytoskeleton-regulating proteins that mediate the formation of intercellular junctions. Their localized activation by Rho GEFs (guanine-nucleotide exchange factors) and the selective activation of downstream effectors have emerged as areas of active research in the cell adhesion field. We reported recently that the Rho-specific GEFs Syx (Synectin-binding RhoA exchange factor) and TEM4 (Tumor Endothelial Marker 4) are both essential for endothelial junction maturation and barrier function. Syx is recruited to cell contacts via its C-terminal PDZ binding motif and it's interaction with Mupp1 and the Crumbs polarity complex, while the junctional localization of TEM4 requires it's N-terminal domain and interaction with the cadherin-catenin complex. Our findings support multiple roles for RhoA in junction formation and maintenance. They also suggest that selective coupling of RhoA activation to Dia1 and/or ROCK signaling is critical for determining endothelial junction integrity.
authors.affiliation: Department of Cancer Biology; Mayo Clinic Comprehensive Cancer Center; Jacksonville, FL, USA.
authors.forename: Siu P
authors.initials: SP
authors.lastname: Ngok
authors.affiliation: Department of Cancer Biology; Mayo Clinic Comprehensive Cancer Center; Jacksonville, FL, USA.
authors.forename: Panos Z
authors.initials: PZ
authors.lastname: Anastasiadis
keywords: GEFs; Rho GTPases; adhesion; cadherin; cell junctions; endothelial; epithelial