Dynamic interaction of VCAM-1 and ICAM-1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes

Abstract

Ezrin, radixin, and moesin (ERM) regulate cortical morphogenesis and cell adhesion by connecting membrane adhesion receptors to the actin-based cytoskeleton. We have studied the interaction of moesin and ezrin with the vascular cell adhesion molecule (VCAM)-1 during leukocyte adhesion and transendothelial migration (TEM). VCAM-1 interacted directly with moesin and ezrin in vitro, and all of these molecules colocalized at the apical surface of endothelium. Dynamic assessment of this interaction in living cells showed that both VCAM-1 and moesin were involved in lymphoblast adhesion and spreading on the endothelium, whereas only moesin participated in TEM, following the same distribution pattern as ICAM-1. During leukocyte adhesion in static or under flow conditions, VCAM-1, ICAM-1, and activated moesin and ezrin clustered in an endothelial actin-rich docking structure that anchored and partially embraced the leukocyte containing other cytoskeletal components such as α-actinin, vinculin, and VASP. Phosphoinositides and the Rho/p160 ROCK pathway, which participate in the activation of ERM proteins, were involved in the generation and maintenance of the anchoring structure. These results provide the first characterization of an endothelial docking structure that plays a key role in the firm adhesion of leukocytes to the endothelium during inflammation.

Regulation of cellular adhesion molecule expression in murine oocytes, peri-implantation and post-implantation embryos

“…Although neither fibronectin [27], [33] nor VCAM-1 [18] is required for implantation, CD49d expression on trophoblast might be able to make use of VCAM-1, were it cyclically expressed in mouse as it is in human maternal decidua [10]. Such interaction may make use of ezrin/radixin/moesin (ERM) proteins crosslinking actin filaments with plasma membranes [34]. The resulting signal transduction could facilitate trophectoderm invasion and further embryonic development.…”

Leukocyte transendothelial migration: A local affair

“…These endothelial structures were first described by Barreiro and colleagues who defined them as docking structures. 66 Other researchers found similar endothelial structures but proposed different names, e.g. transmigratory cups, apical cups, dome structures, ICAM-1-enriched contact areas, or actin dynamic structures.…”

RKIKK Motif in the Intracellular Domain Is Critical for Spatial and Dynamic Organization of ICAM-1: Functional Implication for the Leukocyte Adhesion and Transmigration

“…ICAM-1 has also been known to be associated with ezrin/radixin/moesin (ERM) family members, i.e., ezrin and moesin (Heiska et al, 1998;Barreiro et al, 2002). To test whether truncation of the intracellular domain alters the association of ICAM-1 with the proteins mentioned above, the subcellular distribution of ICAM-1, actin, ezrin, and moesin was analyzed by confocal microscopy in COS-7 cells transfected with wt-IC1_GFP or IC1⌬CTD_GFP.…”

“…Recent reports have demonstrated that ICAM-1/LFA-1 or VCAM-1/VLA-4 interactions promote formation of endothelial projections that surround adherent lymphocytes and are enriched in ICAM-1, VCAM-1, ezrin, and actin (Barreiro et al, 2002;Carman et al, 2003). High-resolution imaging study has also suggested that this structure may function to facilitate and guide TEM by forming a cuplike traction structure called a "transmigratory cup" that is aligned parallel to the direction of transmigration (Carman and Springer, 2004).…”