Immunolocalization and heart levels of GRP94 in the mouse during post-implantation development

Abstract

Glucose-regulated proteins (GRPs), which belong to the highly conserved family of stress proteins, are resident to the endoplasmic reticulum and function as molecular chaperones. Heat shock proteins have been shown to be developmentally regulated, but little work has been done to investigate the expression of GRPs during embryogenesis. Therefore, this study examined the distribution of GRP94 within mouse embryos during the period of organogenesis and characterized levels of GRP94 within the developing heart during organogenesis and late fetal stages. Our results demonstrate that the GRP94 protein is constitutively expressed within mouse embryos during early stages of organogenesis and is localized particularly within the developing heart, neuroepithelium, and surface ectoderm tissues. Positive staining for GRP94 remains within developing heart tissues throughout organogenesis and is found primarily within the atrial and ventricular myocardial cells. Western blot analysis of GRP94 expression demonstrates a significantly higher level of GRP94 in embryonic hearts during early stages of organogenesis than in later stages of organogenesis or the fetal period. These results demonstrate that the stress protein GRP94 is constitutively expressed within specific tissues during post-implantation mouse development and suggest that GRPs may play an important role in the process of myocardial cell differentiation and heart development.

Endoplasmic Reticulum-resident Heat Shock Protein 90 (HSP90) Isoform Glucose-regulated Protein 94 (GRP94) Regulates Cell Polarity and Cancer Cell Migration by Affecting Intracellular Transport

“…GRP94 has been shown to be expressed in oocytes during early embryonic development and at later stages of organogenesis and is lowered to a basal level in adults (61)(62)(63). During tumorigenesis and metastasis, additional proteins are synthesized, which appear to correlate with increased expression of GRP94.…”

GRP94 Is Essential for Mesoderm Induction and Muscle Development Because It Regulates Insulin-like Growth Factor Secretion

“…Expression was also detected in mesoderm cells emerging from the primitive streak (McCormick and Babiarz, 1984). At later stages during organogenesis (E9.5-13.5; embryonic day E0.5 is defined as noon on the day the copulation plug is found), GRP94 was expressed most obviously within the developing heart, neuroepithelium, and surface ectoderm tissues (Barnes and Smoak, 1997). These patterns of expression are likely related to energy needs in the developing embryo: GRP94 expression is highest when and where there is most demand for its function as a stress protein.…”

Targeted Mutation of the Mouse Grp94 Gene Disrupts Development and Perturbs Endoplasmic Reticulum Stress Signaling

“…During mouse embryonic development both GRP94 and GRP78 transcripts are expressed in very early embryos [30] and both proteins are detected at high levels at later stages during organogenesis [31], [32]. Interestingly, heterozygous knockout of Grp78 triggers upregulation of GRP94 and other ER chaperones but not activation of other unfolded protein response (UPR) targets such as CHOP and XBP-1 splicing.…”