Cadherin complexes recruit mRNAs and RISC to regulate epithelial cell signaling

Kourtidis, Antonis; Necela, Brian M.; Lin, Wan Hsin; Lu, Ruifeng; Feathers, Ryan W.; Asmann, Yan W.; Thompson, E. Aubrey; Anastasiadis, Panos Z.

doi:10.1083/jcb.201612125

Cited by 44 publications

(108 citation statements)

References 62 publications

(99 reference statements)

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“…Interestingly our list was not limited to regulators of the intermediate filament cytoskeleton, but also included a number of both microtubule and F-actin interacting proteins; consistent with recent work demonstrating that desmosomes can integrate with both of these networks (25)(26)(27)37). GO term analysis also revealed novel associations with mRNA and miRNA binding proteins ( Fig 2B), an observation previously seen at zonula adherens (38), highlighting that desmosomes may share ancillary molecular functions with adherens junctions in addition to their traditional roles in stabilizing cell-cell attachment and cortical cytoskeleton organization.…”

Section: Quantitative Mass Spectrometry Analysis Of Desmosome-associasupporting

confidence: 83%

Proteomic analysis of the desmosome identifies novel components required for skin integrity

Badu-Nkansah

Lechler

2019

Preprint

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Desmosomes are cell-cell adhesions necessary for the maintenance of tissue integrity in the skin and the heart. While the core components of the desmosome have been identified, peripheral components that modulate canonical desmosome functions or that have noncanonical roles remain largely unexplored. Here we used targeted proximity labeling approaches to elaborate the desmosome proteome in epidermal keratinocytes.Quantitative mass spectrometry analysis identified all core desmosome proteins while uncovering a diverse network of new constituents with broad molecular functions. By individually targeting the inner and outer dense plaques, we additionally define proteins enriched in these subcompartments. We validated a number of these novel desmosomeassociated proteins and find that many show a dependence upon the core desmosomal protein, desmoplakin, for their localization. We further explored the mechanism of localization and function of two novel desmosome-associated adaptor proteins that we identified, Crk and Crkl. These proteins interacted with Dsg1 and require both Dsg1 and desmoplakin for robust cortical localization. Epidermal deletion of both Crk and CrkL in mice resulted in perinatal lethality with defects in desmosome morphology and keratin organization, thus demonstrating the utility of this dataset in identifying novel proteins required for desmosome-dependent epidermal integrity.

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Section: Quantitative Mass Spectrometry Analysis Of Desmosome-associasupporting

confidence: 83%

Proteomic analysis of the desmosome identifies novel components required for skin integrity

Badu-Nkansah

Lechler

2019

Preprint

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“…Subsequently, we detected the expression of various EMT-related proteins, among which the expression levels of vimentin, twist, and snail were regulated by LGR5. However, E-cadherin and N-cadherin [19], which play key roles in the EMT of many tumors, were found not to be regulated by LGR5 after multiple tests in the HSCC we studied. No signi cant changes were observed in the expression of E-cadherin and N-cadherin regardless of LGR5 overexpression or inhibition (data not shown).…”

Section: Discussionmentioning

confidence: 72%

LGR5 promotes invasion and migration by regulating YAP activity in hypopharyngeal squamous cell carcinoma cells

Zhu

Wen

et al. 2020

Preprint

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Background High leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) expression caused by an inflammatory microenvironment was reported to promote tumor proliferation and the epithelial–mesenchymal transition (EMT) in various malignant tumors, but those effects have not been studied in hypopharyngeal squamous cell carcinoma (HSCC) and the molecular mechanism remains unclear. Additionally, YAP/TAZ, an upstream or downstream factor of multiple signaling pathways, can promote tumor proliferation, invasion, and angiogenesis. Our study was aimed to determine whether YAP/TAZ is involved in the regulation of LGR5 expression in the inflammatory microenvironment.Methods We stimulated FaDu cells, a hypopharyngeal squamous cell carcinoma cell line, with inflammatory medium. The expression levels of EMT-related proteins, LGR5, and p-YAP were detected by reverse transcription–polymerase chain reaction, western blotting, and immunofluorescence.Results The results showed that LGR5 expression and the EMT process were significantly enhanced. The expression of EMT-related proteins was up-regulated, while that of p-YAP was decreased. After inhibiting the high LGR5 expression with short interfering RNA, the expression of EMT-related proteins was also down-regulated, while that of p-YAP was significantly increased. The use of verteporfin (VP), an inhibitor of YAP activity that promotes YAP phosphorylation, did not affect LGR5 expression.Conclusions Our findings suggest that the inflammatory microenvironment leads to high LGR5 expression, up-regulating the expression of EMT-related proteins by inhibiting the YAP phosphorylation.

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“…Knockdown of ZBP1, for example, results in the diminished localization of E‐cadherin mRNA and protein at adherens junctions, effectively increasing the invasive properties of MDA231 breast cancer cells . A recent unbiased screen identified more than 500 mRNAs that associate with an adherens junction protein, PLEKHA7, including components of signaling pathways known to locally regulate adherens junctions . These findings suggest that localization of mRNAs to adherens junctions contributes to the dynamic regulation of adhesion and proliferation.…”

Section: The Contribution Of Rna Localization To Acute Cellular Respomentioning

confidence: 99%

RNA localization regulates diverse and dynamic cellular processes

Ryder

Lerit

2018

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At the nexus of specialized cellular responses are localized enrichments of protein activity. The localization of messenger RNA (mRNA) coupled with translational control often plays a crucial role in the generation of protein concentrations at defined subcellular domains. Although mRNA localization is classically associated with large specialized cells, such as neurons and embryos, RNA localization is a highly conserved paradigm of post-transcriptional regulation observed in diverse cellular contexts. Functions of localized mRNAs extend far beyond the well-studied examples of neuronal polarization and developmental patterning. Since the initial discovery of the intracellular localization of cytoskeletal mRNAs within migrating cells, hundreds of mRNAs are now known to be enriched at specific organelles where they contribute to cell function. In this short review, we discuss basic principles regulating RNA localization and consider the contribution of localized mRNA to several essential cellular behaviors. We consider RNA localization as a mechanism with widespread implications for cellular function.

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Cadherin complexes recruit mRNAs and RISC to regulate epithelial cell signaling

Cited by 44 publications

References 62 publications

Proteomic analysis of the desmosome identifies novel components required for skin integrity

Proteomic analysis of the desmosome identifies novel components required for skin integrity

LGR5 promotes invasion and migration by regulating YAP activity in hypopharyngeal squamous cell carcinoma cells

RNA localization regulates diverse and dynamic cellular processes

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