Role of Prostate Apoptosis Response 4 in Translocation of GRP78 from the Endoplasmic Reticulum to the Cell Surface of Trophoblastic Cells
Role of Prostate Apoptosis Response 4 in Translocation of GRP78 from the Endoplasmic Reticulum to the Cell Surface of Trophoblastic Cells
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DOI：
10.1371/journal.pone.0080231
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发表时间：
2013-11-25
期刊：
影响因子：
3.7
通讯作者：
Irion, Olivier
中科院分区：
文献类型：
--
作者：
Cohen, Marie;Ribaux, Pascale;Irion, Olivier
葡萄糖调节蛋白78（GRP 78）是属于热休克蛋白70家族的内质网分子伴侣。GRP 78也存在于滋养层细胞的细胞表面膜上，在那里它与这些细胞的侵袭或融合特性相关。在先兆子痫的细胞滋养层细胞（CTB）中观察到GRP 78从ER重新定位到细胞表面的受损机制，并可能参与先兆子痫的发病机制。在这项研究中，我们已经调查了是否前列腺细胞凋亡反应4（Par-4），一种被确定为伴侣的GRP 78重新定位到前列腺癌细胞的细胞表面的蛋白质，是存在于滋养层细胞，并参与了GRP 78的易位到CTB的细胞表面。Par-4确实存在于滋养层细胞中，其表达与膜GRP 78的表达相关。此外，Par-4的过表达导致GRP 78的细胞表面表达的增加，并且Par-4基因表达的降低降低了GRP 78的细胞表面定位，证实了Par-4在GRP 78从ER向细胞表面的重新定位中的作用。因此，这些细胞的侵袭性被改变。总之，我们发现Par-4在滋养层细胞中表达，并参与GRP 78向细胞表面的转运，从而调节绒毛外CTB的侵袭性。
Glucose-regulated protein 78 (GRP78) is an endoplasmic reticulum (ER) molecular chaperone that belongs to the heat shock protein 70 family. GRP78 is also present on the cell surface membrane of trophoblastic cells, where it is associated with invasive or fusion properties of these cells. Impaired mechanism of GRP78 relocation from ER to the cell surface was observed in preeclamptic cytotrophoblastic cells (CTB) and could take part in the pathogenesis of preeclampsia. In this study, we have investigated whether prostate apoptosis response 4 (Par-4), a protein identified as a partner of GRP78 relocation to the cell surface in prostate cancer cells, is present in trophoblastic cells and is involved in the translocation of GRP78 to the cell surface of CTB. Par-4 is indeed present in trophoblastic cells and its expression correlates with expression of membrane GRP78. Moreover, overexpression of Par-4 led to an increase of cell surface expression of GRP78 and decreased Par-4 gene expression reduced cell surface localization of GRP78 confirming a role of Par-4 in relocation of GRP78 from ER to the cell surface. Accordingly, invasive property was modified in these cells. In conclusion, we show that Par-4 is expressed in trophoblastic cells and is involved in transport of GRP78 to the cell surface and thus regulates invasive property of extravillous CTB.