Wadehra Madhuri, Forbes Ashley, Pushkarna Natasha, Goodglick Lee, Gordon Lynn K, Williams Carmen J, Braun Jonathan
Department of Pathology and Laboratory, University of California, Los Angeles, CA 90095, USA.
Dev Biol. 2005 Nov 15;287(2):336-45. doi: 10.1016/j.ydbio.2005.09.003. Epub 2005 Oct 10.
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.
四跨膜蛋白上皮膜蛋白2（EMP2）最近被确定为胚泡着床所必需的一种子宫内膜蛋白，但其发挥这一作用的机制尚不清楚。在其他细胞类型中，EMP2控制某些种类蛋白质向细胞表面的转运，包括各种整合素亚型（一类与子宫内膜-胚泡相互作用有关的受体）。由于αvβ3整合素是参与胚泡相互作用的一种重要的子宫内膜分子，我们评估了EMP2在体内对人子宫内膜癌细胞系HEC1A和子宫内膜上皮中整合素表达的调节作用。HEC1A细胞中EMP2表达的升高选择性地增加了质膜上αvβ3整合素的表达，并且通过增加细胞与αvβ3配体纤连蛋白的结合来判断其具有功能活性。相反，使用EMP2特异性核酶降低EMP2表达会减少细胞表面αvβ3的表达。在体内也观察到了EMP2对αvβ3整合素的影响，因为使用核酶或短发夹RNA降低EMP2会减少腺上皮和腔上皮中αvβ3整合素的表达。共定位和免疫共沉淀研究表明，EMP2和αvβ3整合素主要以物理关联状态存在。本研究首次证明了EMP2对αvβ3表面表达的影响，并表明在着床窗口期EMP2介导整合素αvβ3的表面转运可能是其在子宫内膜-胚泡相互作用中发挥作用的一种机制。
