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

By O. Barreiro, María Yáñez-Mó, J. Serrador, M. Montoya, M. Vicente-Manzanares, R. Tejedor, H. Furthmayr, F. Sánchez‐Madrid. Journal of Cell Biology, 2002

659 citations recorded by the source corpus.

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.

Subfields: Hematology, Immunology and Allergy

View Paper: https://www.semanticscholar.org/paper/f048c3eb36ae3373f28875aad7612e2010928e5a

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Hematology

1. Werner Müller
2. Asrar B. Malik
3. N. Borregaard

In Immunology and Allergy

1. P. Kubes
2. Werner Müller
3. R. Alon
4. S. Nourshargh
5. C. Carman
6. N. Borregaard
7. B. Engelhardt
8. T. Springer

Citations in the corpus

• Reactive Oxygen Species in Inflammation and Tissue Injury (2014, positive): “Transmigratory cups are microvilli-like projections that surround leukocytes and help in efficient transendothelial migration of leukocytes (24, 52).”
• Getting to the site of inflammation: the leukocyte adhesion cascade updated (2007, background): “Adherent leukocytes can induce the formation of 'docking structures' or 'transmigratory cups', which are endothelial-cell projections rich in ICAM1 and VCAM1 and cytoplasmic molecules such as ERM (ezrin, radixin and moesin) proteins and cytoskeletal components (such as vinculin, α-actinin and talin-”
• Neutrophils, from marrow to microbes. (2010, background): “…protrusions called apical cups or docking structures where ICAM-1, and VCAM-1 (a ligand for b 1 integrins) are concentrated (van Buul et al., 2007; Barreiro et al., 2002), most likely via ezrin, radixin, and moesin that, when activated, tether ICAM-1 and V-CAM-1 to the actin cytoskeleton (Sato et…”
• A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them (2004, background): “However, in one of them it was interpreted that the endothelial projection structures likely functioned in adhesion strengthening and were incompatible with diapedesis and therefore would be required to disassemble before diapedesis could proceed (Barreiro et al., 2002).”
• The Neutrophil's Role During Health and Disease. (2019, background): “Neutrophils themselves are also able to release annexin 1 which interacts with the endothelium (22).”
• Mechanisms of Leukocyte Transendothelial Migration (2011, background): “However, for transcellular migration, as for paracellular migration, some investigators (6, 8, 69, 73) did not observe the docking structures or transmigratory cups formed by projections of ICAM-1 above the plane of the endothelial cell membrane that were reported by others (9, 10).”
• Immune cell migration in inflammation: present and future therapeutic targets (2005, background): “Both routes demonstrate a proactive function for both apical and junctional endothelial ICAM-1 and VCAM-1, whose expression is differentially increased at specific sites of inflammatio”
• Blood–brain Barrier: Structural Components and Function Under Physiologic and Pathologic Conditions (2006, background): “Docking structures involve formation of microvilli-like projections that embrace adherent leukocyte (Carman et al. 2003) and express clustered VCAM-1, ICAM-1, and proteins erzin and moesin (Barreiro et al. 2002).”
• The blood–brain and the blood–cerebrospinal fluid barriers: function and dysfunction (2009, background): “Vesiculo-vacuolar organelles or caveolae have been suggested to be involved in regulating this transcellular diapedesis of leukocytes [86, 87].”