The cytoplasmic tail of PECAM contains a recognition motif for trafficking into and out of the Lateral Border Recycling Compartment (LBRC)

Abstract

A novel membrane compartment in endothelial cells (EC), the LBRC, contains PECAM, CD99, and JAM‐A‐‐molecules that participate in leukocyte transendothelial migration (TEM). Membrane trafficking from the LBRC to surround the leukocyte is a critical event in the TEM. How a subset of molecules is selected to enter the LBRC from the cell borders is not known. Since Y663F mutation of PECAM’s cytoplasmic tail disrupts its LBRC trafficking ability without interfering with PECAM signaling, we hypothesized that the cytoplasmic tail of PECAM might contain a motif for the trafficking of PECAM into and out of the LBRC. To test this we constructed chimeras with the extracellular domain of CD25, a membrane protein normally not expressed on EC, and the cytoplasmic domain of PECAM. When transfected into EC, wild‐type CD25 shows diffuse distribution on the plasma membrane. However, CD25 bearing the cytoplasmic domain of PECAM localizes to the cell borders. Furthermore, this chimera constitutively recycles from the LBRC to the cell junctions with the same kinetics as PECAM. Our data suggest the cytoplasmic tail of PECAM contains a recognition motif for trafficking into and out of the LBRC. Support: NIH R01 HL046489.