Segregation of VE-cadherin from the LBRC depends on the ectodomain sequence required for homophilic adhesion

Gong Feng, David P. Sullivan, Fei Han, William A. Muller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The lateral border recycling compartment (LBRC) is a reticulum of perijunctional tubulovesicular membrane that is continuous with the plasmalemma of endothelial cells and is essential for efficient transendothelial migration (TEM) of leukocytes. The LBRC contains molecules involved in TEM, such as PECAM, PVR and CD99, but not VE-cadherin. Despite its importance, how membrane proteins are included in or excluded from the LBRC is not known. Immunoelectronmicroscopy and biochemical approaches demonstrate that inclusion into the LBRC is the default pathway for transmembrane molecules present at endothelial cell borders. A chimeric molecule composed of the extracellular domain of VEcadherin and cytoplasmic tail of PECAM (VE-CAD/PECAM) did not enter the LBRC, suggesting that VE-cadherin was excluded by a mechanism involving its extracellular domain. Deletion of the homophilic interaction domain EC1 or the homophilic interaction motif RVDAE allowed VE-CAD/PECAM and even native VEcadherin to enter the LBRC. Similarly, treatment with RVDAE peptide to block homophilic VE-cadherin interactions allowed endogenous VE-cadherin to enter the LBRC. This suggests that homophilic interactions of VE-cadherin stabilize it at cell borders and prevent entry into the LBRC.

Original languageEnglish (US)
Pages (from-to)576-588
Number of pages13
JournalJournal of cell science
Volume128
Issue number3
DOIs
StatePublished - 2015

Keywords

  • Endothelial cells
  • Lateral border recycling compartment
  • Membrane compartmentalization
  • Sorting signals
  • VE-cadherin

ASJC Scopus subject areas

  • Cell Biology

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