Human placenta and trophoblasts simultaneously express three isoforms of atypical protein kinase-c

Shaha, Sumaiyah; Patel, Khushali; Saadat, Saba; Panahi, Sareh; Almeida, Monique Marylin Alves de; Voronova, Anastassia; Riddell, Meghan

doi:10.1016/j.placenta.2022.01.015

Cited by 8 publications

(27 citation statements)

References 12 publications

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“…Our initial studies examining aPKC isoforms in the human placenta revealed an apparent lack of anti-aPKC-ι or anti-aPKC-ζ/ζ III signal accumulation at the ST apical membrane in early first trimester placental samples(24). In other cell types, apical localization is required for aPKC’s to regulate apical-basal polarity, as mentioned above.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, we first performed colocalization analyses using antibodies targeting aPKC-ι or aPKC-ζ isoforms (which we previously validated to recognize aPKC-ζ and aPKC-ζ III (24)) and an anti-ezrin antibody, an established ST apical membrane marker in third trimester placenta(32). As we observed previously(24), the anti-aPKC-ι signal was weak and largely diffuse within the ST from 4-6 weeks gestation (Supplementary Figure 1A). There was also a lack of consistent apical accumulation of anti-ezrin signal at the ST apical surface despite a highly accumulated and complex pattern of anti-β-actin signal in the apical region (Supplementary Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

“…Term placental cytotrophoblasts were isolated according to previously published methods(24, 85). To obtain in vitro differentiated syncytiotrophoblasts, isolated cytotrophoblast progenitor cells were seeded into 6 well plates and cultured in IMDM+10%FCS+ Penicillin-streptomycin and incubated for 4hrs at 37°C 5%CO 2 .…”

Section: Methodsmentioning

confidence: 99%

“…Term placental cytotrophoblasts were isolated according to previously published methods(24, 85). Briefly, placentas were trimmed of basal plate and decidual tissue, washed extensively to remove blood, minced, and digested via serial trypsin DNase digestion (Gibco).…”

Section: Methodsmentioning

confidence: 99%

“…The copyright holder for this preprint (which this version posted July 1, 2022. ; https://doi.org/10.1101/2022.06. 30.498172 doi: bioRxiv preprint truncated PRKCZ encoded isoform -aPKC-ζ III (24). aPKC-ζ III lacks the N-terminal PB-1 domain required for Par-6 binding (24,25).…”

Section: Introductionmentioning

confidence: 99%

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Loss of polarity regulators initiates gasdermin E mediated pyroptosis in human maternal fetal interface trophoblasts

Patel

Nguyen

Shaha

et al. 2022

Preprint

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The syncytiotrophoblast is a single giant multinucleate epithelial cell that forms the maternal surface of the human placenta and is bathed in maternal blood. It acts as a physical barrier between the maternal and fetal compartments and facilitates nutrient and waste exchange. As such, syncytiotrophoblast dysfunction is a key feature of pregnancy pathologies, such as preeclampsia. An understudied feature of dysfunctional syncytiotrophoblast is the loss of apical microvilli. But a paucity of data exists about the mechanisms regulating syncytiotrophoblast microvilli maintenance. Atypical protein kinase-c (aPKC) isoforms are evolutionarily conserved apical polarity regulators, which are known to play a role in the regulation of intestinal microvilli. Thus, we hypothesized that aPKC isoforms regulate syncytiotrophoblast microvilli and apical surface structure. Using human placental explant culture and primary human trophoblasts, we found that aPKCs regulate the structure, permeability, and endocytic function of the syncytiotrophoblast apical surface in a spatially restricted manner. A heightened inflammatory environment is often involved in the pathogenesis of placental pathologies, and the pro-inflammatory cytokine TNF-α can decrease aPKC-ι expression in intestinal cells. Here we establish that TNF-α exposure leads to reduced expression of the aPKC-ι isoform in syncytiotrophoblast and profoundly alters ST apical structure and permeability via regionalized pyroptosis, a highly pro-inflammatory form of cell death. Therefore, this is the first work to identify a regulator of apical-surface structure and the induction of the pyroptotic cascade at the maternal surface of the human placenta.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Loss of polarity regulators initiates gasdermin E mediated pyroptosis in human maternal fetal interface trophoblasts

Patel

Nguyen

Shaha

et al. 2022

Preprint

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Cell polarity signaling in the regulation of syncytiotrophoblast homeostasis and inflammatory response

2023

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Siglec-6 mediates the uptake of extracellular vesicles through a noncanonical glycolipid binding pocket

et al. 2023

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Immunomodulatory Siglecs are controlled by their glycoprotein and glycolipid ligands. Siglec-glycolipid interactions are often studied outside the context of a lipid bilayer, missing the complex behaviors of glycolipids in a membrane. Through optimizing a liposomal formulation to dissect Siglec–glycolipid interactions, it is shown that Siglec-6 can recognize glycolipids independent of its canonical binding pocket, suggesting that Siglec-6 possesses a secondary binding pocket tailored for recognizing glycolipids in a bilayer. A panel of synthetic neoglycolipids is used to probe the specificity of this glycolipid binding pocket on Siglec-6, leading to the development of a neoglycolipid with higher avidity for Siglec-6 compared to natural glycolipids. This neoglycolipid facilitates the delivery of liposomes to Siglec-6 on human mast cells, memory B-cells and placental syncytiotrophoblasts. A physiological relevance for glycolipid recognition by Siglec-6 is revealed for the binding and internalization of extracellular vesicles. These results demonstrate a unique and physiologically relevant ability of Siglec-6 to recognize glycolipids in a membrane.

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Human placenta and trophoblasts simultaneously express three isoforms of atypical protein kinase-c

Cited by 8 publications

References 12 publications

Loss of polarity regulators initiates gasdermin E mediated pyroptosis in human maternal fetal interface trophoblasts

Loss of polarity regulators initiates gasdermin E mediated pyroptosis in human maternal fetal interface trophoblasts

Cell polarity signaling in the regulation of syncytiotrophoblast homeostasis and inflammatory response

Siglec-6 mediates the uptake of extracellular vesicles through a noncanonical glycolipid binding pocket

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