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Published 24 June 2002. doi:10.1083/jcb.200112126
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© The Rockefeller University Press, 0021-9525/2002/6/1233 $5.00
The Journal of Cell Biology, Volume 157, Number 7, June 24, 2002 1233-1245

Article

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

Olga Barreiro1, María Yáñez-Mó1, Juan M. Serrador1, María C. Montoya1, Miguel Vicente-Manzanares1, Reyes Tejedor1, Heinz Furthmayr2 and Francisco Sánchez-Madrid1

1 Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain
2 Department of Pathology, Stanford University, Stanford, CA 94305

Address correspondence to Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, C/Diego de León 62, 28006 Madrid, Spain. Tel.: 34-91-309-2115. Fax: 34-91-520-2374. E-mail: fsanchez{at}hlpr.insalud.es

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 {alpha}-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.

Key Words: ERM; VCAM-1; ICAM-1; leukocyte adhesion and transendothelial migration; docking structure


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