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ERM proteins may regulate deactivation of PAF‐induced endothelial hyperpermeability
Author(s) -
Mujica Patricio,
Durán Walter N.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.707.8
Subject(s) - moesin , microbiology and biotechnology , radixin , phosphorylation , chemistry , platelet activating factor , vascular permeability , ezrin , endothelium , platelet activation , cytoskeleton , platelet , biology , biochemistry , immunology , cell , endocrinology
Endothelial hyperpermeability is a hallmark of inflammation. Endothelial barrier function is restored after a period of hyperpermeability, but the mechanisms that deactivate hyperpermeability are largely unknown. Exchange protein activated by cAMP (Epac) is emerging as a possible deactivating/restorative factor in the endothelium. Epac localization, which is modulated by Ezrin/Radixin/Moesin (ERM) proteins, may determine its function due to cellular compartmentalization of cAMP signaling. We report preliminary results testing the hypothesis that ERM proteins facilitate deactivation of hyperpermeability by localizing Epac to the plasma membrane. We demonstrated association between Epac and ERM proteins in human microvascular endothelial cells (HMVEC) by co‐immunoprecipitation. Depletion of Radixin and Moesin by siRNA increased baseline HMVEC monolayer permeability to macromolecules, as well as PAF (platelet‐activating factor)‐induced permeability. Inhibition of PKC abrogated PAF‐induced ERM phosphorylation. We propose that deactivation of PAF‐stimulated hyperpermeability is implemented in a time‐orchestrated manner, by PAF‐induced activation of ERM proteins, which locate Epac to the plasma membrane promoting its interactions with endothelial junctional proteins. (Supported by NIH grants 5RO1 HL070634 & 5RO1 HL088479).