Epithelial membrane protein-2 regulates surface expression of alphavbeta3 integrin in the endometrium.
Epithelial membrane protein-2 regulates surface expression of alphavbeta3 integrin in the endometrium.
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上皮膜蛋白 2 调节子宫内膜中 αvβ3 整合素的表面表达。
DOI：
10.1016/j.ydbio.2005.09.003
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Braun,Jonathan
中科院分区：
文献类型：
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作者：
Wadehra,Madhuri;Forbes,Ashley;Pushkarna,Natasha;Goodglick,Lee;Gordon,LynnK;Williams,CarmenJ;Braun,Jonathan
四跨膜蛋白上皮膜蛋白-2（EMP 2）最近被鉴定为胚泡着床所必需的子宫内膜蛋白，但其作用机制尚不确定。在其他细胞类型中，EMP 2控制某些类型的蛋白质向细胞表面的递送，包括各种整合素同种型（一类涉及胚胎-胚泡相互作用的受体）。由于αvβ3整合素是参与胚泡相互作用的重要子宫内膜分子，我们评估了EMP 2在体内调节HEC 1A子宫内膜细胞系和子宫内膜上皮中整合素表达的作用。HEC 1A细胞中EMP 2表达的升高选择性地增加了质膜上αvβ3整联蛋白的表达，并且通过增加细胞与αvβ3配体纤连蛋白的结合来判断其功能。相反，使用EMP 2特异性核酶降低EMP 2表达会降低细胞αvβ3表面表达。在体内也观察到EMP 2对αvβ3整联蛋白的影响，因为使用核酶或短发夹RNA减少EMP 2会降低子宫腺上皮和子宫腔上皮中αvβ3整联蛋白的表达。共定位和免疫共沉淀研究表明，EMP 2和αvβ3整合素主要以物理缔合状态存在。本研究首次证实了EMP 2对αvβ3表面表达的影响，并表明在着床窗口期EMP 2对整合素αvβ3的表面运输可能是其在囊胚-囊胚相互作用中的需求机制。
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 αvβ3 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 αvβ3 integrin on the plasma membrane and was functional as judged by increased cell binding to an αvβ3 ligand, fibronectin. Conversely, reduction in EMP2 expression using an EMP2 specific ribozyme decreased the cell αvβ3 surface expression. The influence of EMP2 on αvβ3 integrin was also observed in vivo as reduction of EMP2 using ribozymes or short hairpin RNA diminished αvβ3 integrin expression in glandular and luminal uterine epithelium. Colocalization and coimmunoprecipitation studies suggested that EMP2 and αvβ3 integrin predominantly exist in a physically associated state. This study demonstrates for the first time the influence of EMP2 on αvβ3 surface expression and suggests that surface trafficking of integrin αvβ3 by EMP2 during the window of implantation may be a mechanism for its requirement in endometrial–blastocyst interaction.