Export Control: Post-transcriptional Regulation of the COPII Trafficking Pathway

Bisnett, Brittany; Condon, Brett M; Lamb, Caitlin H.; Georgiou, George R.; Boyce, Michael

doi:10.3389/fcell.2020.618652

Cited by 14 publications

(14 citation statements)

References 195 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have shown that several genes and gene sets with known links to NTDs are dysregulated in placentae from fetuses with isolated SB. The COPII pathway was downregulated in case placentae and is a critical regulator of forward trafficking of proteins and lipids from the ER 32 . Disruptions in COPII‐mediated vesicular ER‐to‐Golgi transport have been linked to SB via the transporting role of COPII 33 .…”

Section: Discussionmentioning

confidence: 99%

Fetal spina bifida associates with dysregulation in nutrient‐sensitive placental gene networks: Findings from a matched case–control study

White,

Arif‐Pardy,

Van Mieghem

et al. 2024

Clinical Translational Sci

View full text Add to dashboard Cite

To improve outcomes in fetuses with spina bifida (SB), better understanding is needed of the molecular drivers of SB and its comorbidities. Pregnant people carrying a fetus with isolated SB (cases; n=12) or a fetus with no congenital anomalies (controls; n=21) were recruited at Mount Sinai Hospital, Toronto. Clinical data and placental samples were collected. Placental transcriptome was sequenced (Clariom DTM microarray) and a nutrient‐focused gene expression analysis pipeline was applied to determine whether fetal SB associates with placental dysfunction. Of the 391 differentially expressed genes (DEGs) in cases, 11% (n=42) had at least one nutrient cofactor, including B vitamins (n=7 genes), iron/heme (n=6), and zinc (n=11). Cases had dysregulation in genes not previously known to associate with SB, and in placental genes that have known links to SB but have not been previously identified in the placenta. Cases also had downregulated nutrient transport and upregulated branching angiogenesis and immune/inflammatory processes. Five nutrient‐dependent transcription regulators, collectively predicted to target 46% of DEGs in cases, were identified and were most commonly dependent on B vitamins (n=3) and zinc (n=2). Placental gene expression changes were most acute in cases with poor growth. Placentae from fetuses with SB have dysregulation in several gene networks, including those that are sensitive to multiple micronutrients beyond the well‐known folic acid. An improved understanding of placental phenotype in fetuses with SB may help identify novel mechanisms associated with comorbidities in fetuses with SB, and reveal new targets to improve fetal outcomes in this population.

show abstract

Section: Discussionmentioning

confidence: 99%

Fetal spina bifida associates with dysregulation in nutrient‐sensitive placental gene networks: Findings from a matched case–control study

White,

Arif‐Pardy,

Van Mieghem

et al. 2024

Clinical Translational Sci

View full text Add to dashboard Cite

show abstract

“…We have shown for the first time that several genes and gene pathways with known links to NTDs are dysregulated in placentae from fetuses with isolated SB. The COPII pathway, which was downregulated in case placentae, is a critical regulator of forward trafficking of proteins and lipids from the endoplasmic reticulum (ER) 56 . Disruptions in COPIImediated vesicular ER-to-Golgi transport have been linked to SB via the role of COPII in transporting key components of the planar cell polarity (non-canonical Wnt) pathway [57][58][59] .…”

Section: Discussionmentioning

confidence: 99%

Fetal spina bifida associates with dysregulation in nutrient-sensitive placental gene networks: findings from a matched case-control study

White

Arif-Pardy

Mieghem

et al. 2023

Preprint

View full text Add to dashboard Cite

To improve outcomes of fetuses with spina bifida (SB), better knowledge is needed on the molecular drivers of SB and its comorbidities. We have recently shown in historical data that SB often associates with reduced fetal growth. We here use placental transcriptome sequencing and a novel nutrient-focused analysis pipeline to determine whether this association is due to placental dysfunction. We show that fetuses with SB have dysregulation in placental gene networks that play a role in nutrient transport, branching angiogenesis, and immune/inflammatory processes. Several of these networks are sensitive to multiple micronutrients, other than the well-known folic acid, and this deserves further investigation. An improved understanding of placental phenotype in fetuses with SB may help identify novel mechanisms associated with SB and its comorbidities, and reveal new targets to improve fetal outcomes in this population.

show abstract

“…A glycoproteome analysis recently identified 55 O-mannosylation sites in Sed4 as well as 15 O-mannosylation and one N-glycosylation sites in Sec12 ( Neubert et al, 2016 ). Recent studies have demonstrated the importance of post-translational modifications in the regulation of COPII proteins, such as phosphorylation and O-glycosylation in the cytosol ( Bisnett et al, 2021 ). However, the functions of glycosylation of Sed4 and Sec12 are unknown.…”

Section: Introductionmentioning

confidence: 99%

Sec16 and Sed4 interdependently function as interaction and localization partners at ER exit sites

Yorimitsu

Sato

2023

Journal of Cell Science

View full text Add to dashboard Cite

COPII proteins assemble at ER exit sites (ERES) to form transport carriers. The initiation of COPII assembly in the yeast Saccharomyces cerevisiae is triggered by the ER membrane protein Sec12. Sec16, which plays a critical role in COPII organization, localizes to ERES independently of Sec12. However, the mechanism underlying Sec16 localization is poorly understood. Here, we show that a Sec12 homolog, Sed4, is concentrated at ERES and mediates ERES localization of Sec16. We found that the interaction between Sec16 and Sed4 ensures their correct localization to ERES. Loss of the interaction with Sec16 leads to redistribution of Sed4 from the ERES specifically to high-curvature ER areas, such as the tubules and edges of the sheets. The luminal domain of Sed4 mediates this distribution, which is required for Sed4, but not for Sec16, to be concentrated at ERES. We further show that the luminal domain and its O-mannosylation are involved in the self-interaction of Sed4. Our findings provide insight into how Sec16 and Sed4 function interdependently at ERES.

show abstract

Export Control: Post-transcriptional Regulation of the COPII Trafficking Pathway

Cited by 14 publications

References 195 publications

Fetal spina bifida associates with dysregulation in nutrient‐sensitive placental gene networks: Findings from a matched case–control study

Fetal spina bifida associates with dysregulation in nutrient‐sensitive placental gene networks: Findings from a matched case–control study

Fetal spina bifida associates with dysregulation in nutrient-sensitive placental gene networks: findings from a matched case-control study

Sec16 and Sed4 interdependently function as interaction and localization partners at ER exit sites

Contact Info

Product

Resources

About