RESUMO
Selenoprotein T (SelT) is a recently characterized thioredoxin-like protein whose expression is very high during development, but is confined to endocrine tissues in adulthood where its function is unknown. We report here that SelT is required for adaptation to the stressful conditions of high hormone level production in endocrine cells. Using immunofluorescence and TEM immunogold approaches, we find that SelT is expressed at the endoplasmic reticulum membrane in all hormone-producing pituitary cell types. SelT knockdown in corticotrope cells promotes unfolded protein response (UPR) and ER stress and lowers endoplasmic reticulum-associated protein degradation (ERAD) and hormone production. Using a screen in yeast for SelT-membrane protein interactions, we sort keratinocyte-associated protein 2 (KCP2), a subunit of the protein complex oligosaccharyltransferase (OST). In fact, SelT interacts not only with KCP2 but also with other subunits of the A-type OST complex which are depleted after SelT knockdown leading to POMC N-glycosylation defects. This study identifies SelT as a novel subunit of the A-type OST complex, indispensable for its integrity and for ER homeostasis, and exerting a pivotal adaptive function that allows endocrine cells to properly achieve the maturation and secretion of hormones.
Assuntos
Hormônio Adrenocorticotrópico/metabolismo , Corticotrofos/metabolismo , Degradação Associada com o Retículo Endoplasmático , Hexosiltransferases/genética , Proteínas de Membrana/genética , Selenoproteínas/genética , Transdução de Sinais , Hormônio Adrenocorticotrópico/genética , Animais , Sistemas CRISPR-Cas , Linhagem Celular , Corticotrofos/citologia , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/ultraestrutura , Edição de Genes , Regulação da Expressão Gênica , Glicosilação , Hexosiltransferases/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Microssomos/metabolismo , Hipófise/citologia , Hipófise/metabolismo , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , RNA Interferente Pequeno , Selenoproteínas/antagonistas & inibidores , Selenoproteínas/metabolismo , Técnicas do Sistema de Duplo-HíbridoRESUMO
The coronavirus pandemic (COVID-19) has had an immense impact on humanity in every aspect of life. Governments around the world have mandated movement restrictions, including in the Moroccan government, in which unfortunately the pandemic continues to propagate and causes serious problems for public health and economic activities in the Kingdom. As a major factor in the fight against the spread of COVID-19, the Moroccan government has undertaken major efforts to ensure the availability of the COVID-19 vaccines for all citizens. These valuable efforts resulted in initiation of the vaccination campaign, which started on February 14, 2021. As vaccination was voluntary, identifying the factors promoting citizen's intention to take the vaccine against COVID-19 may help government to take additional precautions to address the propagation of COVID-19, and ensure a return to normal life. Hence, this data article aims to identify factors influencing the Moroccan citizens to get a vaccine for COVID-19. The data were collected using an online questionnaire among Moroccan citizens. In addition, the Partial Least Squares Structural Equation Modeling technique was adopted in order to analyze the collected dataset.
RESUMO
Several cues including pituitary adenylate cyclase-activating polypeptide (PACAP), which acts through cAMP stimulation, specify the conversion of sympathoadrenal (SA) precursors toward different cell phenotypes by promoting their survival and differentiation. Selenoprotein T (SELENOT) is a PACAP-stimulated ER oxidoreductase that exerts an essential antioxidant activity and whose up-regulation is associated with SA cell differentiation. In the present study, we investigated the transcriptional cascade elicited by PACAP/cAMP to trigger SELENOT gene transcription during the conversion of PC12 cells from SA progenitor-like cells toward a neuroendocrine phenotype. Unexpectedly, we found that PACAP/cAMP recruits the canonical pathway that regulates mitochondrial function in order to elicit SELENOT gene transcription and the consequent antioxidant response during PC12 cell differentiation. This cascade involves LKB1-mediated AMPK activation in order to stimulate SELENOT gene transcription through the PGC1-α/NRF-1 complex, thus allowing SELENOT to promote PACAP-stimulated neuroendocrine cell survival and differentiation. Our data reveal that a PACAP and cAMP-activated AMPK-PGC-1α/NRF-1 cascade is critical for the coupling of oxidative stress tolerance, via SELENOT gene expression, and mitochondrial biogenesis in order to achieve PC12 cell differentiation. The data further highlight the essential role of SELENOT in cell metabolism during differentiation.