Secreted Frizzle-Related Protein (sFRP4) can Abrogate Pregnancy - A New Dimension in its Biological Role

Abstract

Successful implantation is dependent on precisely orchestrated and reciprocal signaling between the implanting blastocyst and the receptive uterus. A key signaling mechanism that is operative during implantation is the Wnt/ Beta - catenin signaling pathway. Secreted frizzled-related proteins (sFRPs) are reported to be antagonist to these pathways and are group of secreted glycoproteins, structurally similar to Wnt receptors [frizzled (FZD) proteins] but lack the transmembrane domains. SFRPs inhibit Wnt action through competitive binding to the ligandbinding domain of the frizzled receptor complex. In silico analysis using PSORTII has revealed mouse sFRP4 to be predominantly mitochondrial (43.5%) and nuclear (34.8%) and not extracellular like human sFRP4 (44.4 %). Our western blotting and immunohistochemical studies unraveled the sub-cellular localization of the sFRP4 molecule and its significant presence in the nucleus and the mitochondrial fraction during the peri-implantation stage. The nuclear presence of sFRP4 during pregnancy adds new dimension to its potential modes of action and biological function. Studies are underway to explore the structure and function of sFRP4 using molecular modeling.