Expression of the prion-like protein Shadoo in the developing mouse embryo

Young, Rachel; Bouet, Stéphan; Polyte, Jacqueline; Guillou, Sandrine Le; Passet, Bruno; Vilotte, Marthe; Castille, Johan; Béringue, Vincent; Provost, Fabienne Le; Laude, Hubert; Vilotte, Jean Luc

doi:10.1016/j.bbrc.2011.11.021

Cited by 8 publications

(5 citation statements)

References 16 publications

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“…Prnp gene expression was also observed in human trophoblast cells (Alfaidy et al, 2013 ) and that of Sprn indirectly suspected to occur in mouse trophectoderm (Passet et al, 2012 ). We have detected Sprn and Prnd gene expressions in extra-embryonic tissues of mouse embryos at E10.5 and E13.5 (our unpublished observation and Young et al, 2011 ). In sheep, Prnp transcripts were also detected in mature and immature oocytes and at the morula stage (Thumdee et al, 2007 ) while in mouse, the recent sequencing of single oocytes revealed that the three genes are potentially expressed at very low amounts in such cells (Reich et al, 2012 ).…”

Section: Prion Protein Gene Family Expression In Extra-embryonic Tissmentioning

confidence: 53%

The prion protein family: a view from the placenta

Makzhami

Passet

Halliez

et al. 2014

Front. Cell Dev. Biol.

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Based on its developmental pattern of expression, early studies suggested the implication of the mammalian Prion protein PrP, a glycosylphosphatidylinositol-anchored ubiquitously expressed and evolutionary conserved glycoprotein encoded by the Prnp gene, in early embryogenesis. However, gene invalidation in several species did not result in obvious developmental abnormalities and it was only recently that it was associated in mice with intra-uterine growth retardation and placental dysfunction. A proposed explanation for this lack of easily detectable developmental-related phenotype is the existence in the genome of one or more gene (s) able to compensate for the absence of PrP. Indeed, two other members of the Prnp gene family have been recently described, Doppel and Shadoo, and the consequences of their invalidation alongside that of PrP tested in mice. No embryonic defect was observed in mice depleted for Doppel and PrP. Interestingly, the co-invalidation of PrP and Shadoo in two independent studies led to apparently conflicting observations, with no apparent consequences in one report and the observation of a developmental defect of the ectoplacental cone that leads to early embryonic lethality in the other. This short review aims at summarizing these recent, apparently conflicting data highlighting the related biological questions and associated implications in terms of animal and human health.

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Section: Prion Protein Gene Family Expression In Extra-embryonic Tissmentioning

confidence: 53%

The prion protein family: a view from the placenta

Makzhami

Passet

Halliez

et al. 2014

Front. Cell Dev. Biol.

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“…It was indeed reported that alterations of trypsin-like serine protease activities, such as granzymes and PRSS found to be differentially expressed in Prnp KO Sprn KD embryos, could alter both the placental development and neurogenesis [39]. Although Sprn transcriptional regulation appears to be more tightly controlled than that of Prnp in terms of tissue-specificity [8], [21], [24], [40], we could detect Sprn expression in E10.5 extra-embryonic annexes, supporting the suggested role of these genes in the trophoblastic lineage (Figure S3 and [24]). …”

Section: Discussionmentioning

confidence: 99%

“…The developmental regulation of the mouse Prnp gene suggested a possible involvement of PrP in embryogenesis [19] – [22] . The two other prion-related proteins are also expressed in early developmental stages according to the available EST databases and to recent reports [23] , [24] . The hypothesis of an embryonic role of the PrP protein family was recently reinforced by the observation that PrP and Shadoo are required for early mouse embryogenesis, as lethality was observed around E10.5 in Sprn -(Shadoo-encoding gene-)knockdown, Prnp -knockout embryos [25] .…”

Section: Introductionmentioning

confidence: 97%

Prion Protein and Shadoo Are Involved in Overlapping Embryonic Pathways and Trophoblastic Development

et al. 2012

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The potential requirement of either the Prion or Shadoo protein for early mouse embryogenesis was recently suggested. However, the current data did not allow to precise the developmental process that was affected in the absence of both proteins and that led to the observed early lethal phenotype. In the present study, using various Prnp transgenic mouse lines and lentiviral vectors expressing shRNAs that target the Shadoo-encoding mRNA, we further demonstrate the specific requirement of at least one of these two PrP-related proteins at early developmental stages. Histological analysis reveals developmental defect of the ectoplacental cone and important hemorrhage surrounding the Prnp-knockout-Sprn-knockdown E7.5 embryos. By restricting the RNA interference to the trophoblastic cell lineages, the observed lethal phenotype could be attributed to the sole role of these proteins in this trophectoderm-derived compartment. RNAseq analysis performed on early embryos of various Prnp and Sprn genotypes indicated that the simultaneous down-regulation of these two proteins affects cell-adhesion and inflammatory pathways as well as the expression of ectoplacental-specific genes. Overall, our data provide biological clues in favor of a crucial and complementary embryonic role of the prion protein family in Eutherians and emphasizes the need to further evaluate its implication in normal and pathological human placenta biology.

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“…Structurally, each resembles one of the halves of PrP: Dpl being globular and Sho disordered in terms of folds, while both are GPI-anchored and complex glycosylated as PrP [31,46]. Contrary to Dpl, Sho is also primarily expressed in the CNS as PrP C , from the early embryonic stage to the adult state [47][48][49]. It was shown to play a role in embryonic development and tissue formation [50,51] and to likely participate in overlapping embryonic pathways with PrP C , as Sprn mRNA knockdown in Prnp 0/0 mice proved lethal [48].…”

Section: Introductionmentioning

confidence: 99%

Membrane Domain Localization and Interaction of the Prion-Family Proteins, Prion and Shadoo with Calnexin

et al. 2021

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The cellular prion protein (PrPC) is renowned for its infectious conformational isoform PrPSc, capable of templating subsequent conversions of healthy PrPCs and thus triggering the group of incurable diseases known as transmissible spongiform encephalopathies. Besides this mechanism not being fully uncovered, the protein’s physiological role is also elusive. PrPC and its newest, less understood paralog Shadoo are glycosylphosphatidylinositol-anchored proteins highly expressed in the central nervous system. While they share some attributes and neuroprotective actions, opposing roles have also been reported for the two; however, the amount of data about their exact functions is lacking. Protein–protein interactions and membrane microdomain localizations are key determinants of protein function. Accurate identification of these functions for a membrane protein, however, can become biased due to interactions occurring during sample processing. To avoid such artifacts, we apply a non-detergent-based membrane-fractionation approach to study the prion protein and Shadoo. We show that the two proteins occupy similarly raft and non-raft membrane fractions when expressed in N2a cells and that both proteins pull down the chaperone calnexin in both rafts and non-rafts. These indicate their possible binding to calnexin in both types of membrane domains, which might be a necessary requisite to aid the inherently unstable native conformation during their lifetime.

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Expression of the prion-like protein Shadoo in the developing mouse embryo

Cited by 8 publications

References 16 publications

The prion protein family: a view from the placenta

The prion protein family: a view from the placenta

Prion Protein and Shadoo Are Involved in Overlapping Embryonic Pathways and Trophoblastic Development

Membrane Domain Localization and Interaction of the Prion-Family Proteins, Prion and Shadoo with Calnexin

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