Epithelial membrane protein-2 regulates surface expression of alphavbeta3 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 alphavbeta3 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 alphavbeta3 integrin on the plasma membrane and was functional as judged by increased cell binding to an alphavbeta3 ligand, fibronectin. Conversely, reduction in EMP2 expression using an EMP2 specific ribozyme decreased the cell alphavbeta3 surface expression. The influence of EMP2 on alphavbeta3 integrin was also observed in vivo as reduction of EMP2 using ribozymes or short hairpin RNA diminished alphavbeta3 integrin expression in glandular and luminal uterine epithelium. Colocalization and coimmunoprecipitation studies suggested that EMP2 and alphavbeta3 integrin predominantly exist in a physically associated state. This study demonstrates for the first time the influence of EMP2 on alphavbeta3 surface expression and suggests that surface trafficking of integrin alphavbeta3 by EMP2 during the window of implantation may be a mechanism for its requirement in endometrial-blastocyst interaction.
Wadehra
Madhuri
M
Department of Pathology and Laboratory, University of California, Los Angeles, CA 90095, USA.
Forbes
Ashley
A
Pushkarna
Natasha
N
Goodglick
Lee
L
Gordon
Lynn K
LK
Williams
Carmen J
CJ
Braun
Jonathan
J
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D010064:Embryo Implantation; D004717:Endometrium / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D021381:Protein Transport / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism
C486403:EMP2 protein, human; C113388:Emp2 protein, mouse; D005353:Fibronectins; D039302:Integrin alphaVbeta3; D008562:Membrane Glycoproteins; D012333:RNA, Messenger