Synthesis of Proteins in the Placenta

Villee, Claude A.

doi:10.1159/000301047

Cited by 10 publications

(2 citation statements)

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“…Interestingly, the relative abundance of free and endoplasmic reticulum (ER)‐bound ribosomes in cytoplasm of cytotrophoblast and syncytiotrophoblast cells respectively, marks the trophoblast cells as the major locale of placental protein synthesis 5 . It was demonstrated previously that protein synthesis is central to the establishment of the nonproliferative materno‐fetal syncytiotrophoblastic barrier 6,7 . Syncytial protein synthesis aids in equilibrating maternal supply to foetal requirements by promoting cellular transport of nutrients 8 .…”

Section: Introductionmentioning

confidence: 99%

“…5 It was demonstrated previously that protein synthesis is central to the establishment of the nonproliferative materno-fetal syncytiotrophoblastic barrier. 6,7 Syncytial protein synthesis aids in equilibrating maternal supply to foetal requirements by promoting cellular transport of nutrients. 8 Besides, the establishment and maintenance of a successful pregnancy requires secretion of a myriad of placental hormones by regulated biosynthesis of new proteins.…”

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Sequestration of eIF4A by angiomotin: A novel mechanism to restrict global protein synthesis in trophoblast cells

et al. 2020

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Enrichment of angiomotin (AMOT) in the ectoplacental cone of E7.5 murine placenta prompted our investigation on the role of AMOT in trophoblast differentiation. We show here that AMOT levels increased in mouse placenta during gestation and also upon induction of differentiation in trophoblast stem cell ex vivo. Proteomic data unravelling AMOT-interactome in trophoblast cells indicated a majority of AMOT interactors to be involved in protein translation. In-depth analysis of AMOT-interactome led to identification of eukaryotic translation initiation factor 4A (eIF4A) as the most plausible AMOT interactor. Loss of function of AMOT enhanced, whereas, gain in function resulted in decline of global protein synthesis in trophoblast cells. Bioinformatics analysis evaluating the potential energy of AMOT-eIF4A binding suggested a strong AMOT-eIF4A interaction using a distinct groove encompassing amino acid residue positions 238 to 255 of AMOT. Co-immunoprecipitation of AMOT with eIF4A reaffirmed AMOT-eIF4A association in trophoblast cells. Deletion of 238 to 255 amino acids of AMOT resulted in abrogation of AMOT-eIF4A interaction. In addition, 238 to 255 amino acid deletion of AMOT was ineffective in eliciting AMOT's function in reducing global protein synthesis. Interestingly, AMOT-dependent sequestration of eIF4A dampened its loading to the m7-GTP cap and hindered its interaction with eIF4G. Furthermore, enhanced AMOT expression in placenta was associated with intrauterine growth restriction in both rats and humans. These results not only highlight a hitherto unknown novel function of AMOT in trophoblast cells but also have broad biological implications as AMOT might be an inbuilt switch to check protein synthesis in developmentally indispensable trophoblast cells.

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Section: Introductionmentioning

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Sequestration of eIF4A by angiomotin: A novel mechanism to restrict global protein synthesis in trophoblast cells

et al. 2020

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Fetal and NeonatalHPAAxis

Wood

Walker

2015

Comprehensive Physiology

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Stress is an integral part of life. Activation of the hypothalamus-pituitary-adrenal (HPA) axis in the adult can be viewed as mostly adaptive to restore homeostasis in the short term. When stress occurs during development, and specifically during periods of vulnerability in maturing systems, it can significantly reprogram function, leading to pathologies in the adult. Thus, it is critical to understand how the HPA axis is regulated during developmental periods and what are the factors contributing to shape its activity and reactivity to environmental stressors. The HPA axis is not a passive system. It can actively participate in critical physiological regulation, inducing parturition in the sheep for instance or being a center stage actor in the preparation of the fetus to aerobic life (lung maturation). It is also a major player in orchestrating mental function, metabolic, and cardiovascular function often reprogrammed by stressors even prior to conception through epigenetic modifications of gametes. In this review, we review the ontogeny of the HPA axis with an emphasis on two species that have been widely studied-sheep and rodents-because they each share many similar regulatory mechanism applicable to our understanding of the human HPA axis. The studies discussed in this review should ultimately inform us about windows of susceptibility in the developing brain and the crucial importance of early preconception, prenatal, and postnatal interventions designed to improve parental competence and offspring outcome. Only through informed studies will our public health system be able to curb the expansion of many stress-related or stress-induced pathologies and forge a better future for upcoming generations.

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The Placenta: Relevance to Toxicology

Miller

Levin³

1983

Reproductive and Developmental Toxicity of Metals

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Synthesis of Proteins in the Placenta

Cited by 10 publications

References 48 publications

Sequestration of eIF4A by angiomotin: A novel mechanism to restrict global protein synthesis in trophoblast cells

Sequestration of eIF4A by angiomotin: A novel mechanism to restrict global protein synthesis in trophoblast cells

Fetal and NeonatalHPAAxis

The Placenta: Relevance to Toxicology

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