Cellular prion: a novel regulator of decidual cell function at the maternal-fetal interface

Cellular prion (PRNP) is a GPI-anchored extrinsic membrane glycoprotein, which has been implicated in mouse decidualization. However, the molecular function of this protein in mouse decidua is not known. In this article, we have characterized and elucidated the possible role of PRNP in mouse decidua. We demonstrated that PRNP expression is evident on embryonic day (E) 6.5 to E9.5 across the primary decidual zone (PDZ) in the mouse implantation site. As gestation progressed, PRNP continued to be expressed in the receding decidua, up to E17.5. shRNA-mediated knockdown of PRNP on E5.5 through E7.5 led to decreased expression of tight junction proteins (TJPs) in PDZ in vivo. These included Cingulin, Afadin, Catenin-α1, Lethal (2) giant larvae protein homolog 1, Claudin-5, and ICAM1. Furthermore, PRNP-positive decidual cells showed augmented expression of autophagic machinery. PRNP knockdown curtailed expression of autophagy-related genes in decidua in vivo. Our results highlight hitherto unknown novel functions of PRNP: (i) an inducer of TJPs at PDZ, which protects the developing embryo and (ii) a decision-maker protein between life and death in decidual cells.