Targeted Recycling of the Lateral Border Recycling Compartment Precedes Adherens Junction Dissociation during Transendothelial Migration

Annette M. Gonzalez, Bita F. Cyrus, William A. Muller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Leukocyte transendothelial migration (TEM) requires two major events: local dissociation of adherens junctions manifested as gaps in vascular endothelial (VE)-cadherin staining at the site of TEM and targeted trafficking of the lateral border recycling compartment (LBRC) to the site of TEM. However, the association between LBRC recycling and VE-cadherin gaps remains unknown. We found that when targeting of the LBRC is selectively inhibited using established methods, such as a function blocking anti-platelet endothelial cell adhesion molecule 1 antibody, depolymerizing microtubules, or microinjection of an antibody that inhibits kinesin, VE-cadherin gaps do not form around the blocked leukocyte. This is the first time that the LBRC has been implicated in this process. We obtained similar results for neutrophils and monocytes and in studies using live cell imaging microscopy conducted under fluid shear conditions. Depolymerizing microtubules did not affect the ability of leukocytes to induce tyrosine phosphorylation of VE-cadherin. A VE-cadherin double mutant (Y658F, Y731F) expressed in endothelial cells acted as a dominant negative and inhibited VE-cadherin gap formation and TEM, yet targeting of the LBRC still occurred. These data suggest that targeting of the LBRC to the site of TEM precedes VE-cadherin clearance. Recruitment of the LBRC may play a role in clearing VE-cadherin from the site of TEM.

Original languageEnglish (US)
Pages (from-to)1387-1402
Number of pages16
JournalAmerican Journal of Pathology
Volume186
Issue number5
DOIs
StatePublished - May 1 2016

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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