Epithelial membrane protein-2 regulates surface expression of αvβ3 integrin in the endometrium

The four-transmembrane protein epithelial membrane protein-2 (EMP2) was recently identified as an endometrial protein necessary for blastocyst implantation, but the mechanism of this role is uncertain. In other cell types, EMP2 controls delivery of certain classes of proteins to the cell surface, including various integrin isoforms (a class of receptors implicated in endometrial-blastocyst interaction). Since alpha v beta 3 integrin is an important endometrial molecule involved in blastocyst interaction, we evaluated the role of EMP2 in modulating integrin expression in the HEC1A endometrial cell line and endometrial epithelium in vivo. Elevation of EMP2 expression in HEC1A cells selectively increased the expression of alpha v beta 3 integrin on the plasma membrane and was functional as judged by increased cell binding to an alpha v beta 3 ligand, fibronectin. Conversely, reduction in EMP2 expression using an EMP2 specific ribozyme decreased the cell alpha v beta 3 surface expression. The influence of EMP2 on alpha v beta 3 integrin was also observed in vivo as reduction of EMP2 using ribozymes or short hairpin RNA diminished alpha v beta 3 integrin expression in glandular and luminal uterine epithelium. Colocalization and coimmunoprecipitation studies suggested that EMP2 and alpha v beta 3 integrin predominantly exist in a physically associated state. This study demonstrates for the first time the influence of EMP2 on alpha v beta 3 surface expression and suggests that surface trafficking of integrin alpha v beta 3 by EMP2 during the window of implantation may be a mechanism for its requirement in endometrial-blastocyst interaction. (C) 2005 Elsevier Inc. All rights reserved.