Phosphatidic Acid Signals via the Hippo Pathway

Stampouloglou, Eleni; Varelas, Xaralabos

doi:10.1016/j.molcel.2018.10.004

Cited by 3 publications

(1 citation statement)

References 10 publications

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“…S5 B), consistent with the study by Meng et al (2018). Thus our work using op-toPLD lends support to the hypothesis emerging from these two studies that PA indeed has different effects on the Hippo pathway in different contexts and experimental conditions (Stampouloglou and Varelas, 2018;Han et al, 2018b). Future work using optoPLD in combination with other toolsets could reveal the causes and mechanisms underlying the differential roles of PA in modulating Hippo signaling.…”

Section: Discussionsupporting

confidence: 87%

Spatiotemporal control of phosphatidic acid signaling with optogenetic, engineered phospholipase Ds

Tei

Baskin

2020

Journal of Cell Biology

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Phosphatidic acid (PA) is both a central phospholipid biosynthetic intermediate and a multifunctional lipid second messenger produced at several discrete subcellular locations. Organelle-specific PA pools are believed to play distinct physiological roles, but tools with high spatiotemporal control are lacking for unraveling these pleiotropic functions. Here, we present an approach to precisely generate PA on demand on specific organelle membranes. We exploited a microbial phospholipase D (PLD), which produces PA by phosphatidylcholine hydrolysis, and the CRY2–CIBN light-mediated heterodimerization system to create an optogenetic PLD (optoPLD). Directed evolution of PLD using yeast membrane display and IMPACT, a chemoenzymatic method for visualizing cellular PLD activity, yielded a panel of optoPLDs whose range of catalytic activities enables mimicry of endogenous, physiological PLD signaling. Finally, we applied optoPLD to elucidate that plasma membrane, but not intracellular, pools of PA can attenuate the oncogenic Hippo signaling pathway. OptoPLD represents a powerful and precise approach for revealing spatiotemporally defined physiological functions of PA.

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Section: Discussionsupporting

confidence: 87%

Spatiotemporal control of phosphatidic acid signaling with optogenetic, engineered phospholipase Ds

Tei

Baskin

2020

Journal of Cell Biology

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Regulation of Hippo Signaling by Mechanical Signals and the Cytoskeleton

Zhang

Wang

Gao

et al. 2020

DNA and Cell Biology

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YAP‑mediated crosstalk between the Wnt and Hippo signaling pathways (Review

Jiang

Zhang

et al. 2020

Mol Med Rep

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Yes-associated protein (YaP) acts as a transcriptional co-activator in gene expression and cell proliferation control by binding to the transcriptional factor Tea domain (Tead) of the Hippo signaling pathway in the nucleus, and also acts as a regulator by binding to another transcriptional co-activator, β-catenin of the Wnt signaling pathway. Whether YaP preferentially acts as a transcriptional co-regulator of the activity of the Hippo signaling pathway or as a regulator in the Wnt signaling pathway depends on the cell type. nuclear YaP upregulates the expression of β-catenin, while cytoplasmic YaP has a negative effect on this expression. The present mini-review focused on the important roles of YaP and further discussed the cross-links between the Wnt and Hippo signaling pathways. The Wnt and Hippo signaling pathways are both related to the development of fibrosis or cancer. The current review discussed treatment approaches for these conditions based on the two pathways. YaP, the intersection of these two signaling pathways, has the potential to be developed as a novel treatment target, according to previous basic studies on fibroblasts and cancer cells. Contents1. introduction 2. YaP complex in the Hippo and Wnt signaling pathway 3. YaP serves a key role in controlling organ size 4. YaP is a transcriptional co-activator or a regulator depending on the cell type 5. YAP has both negative and positive influences on the Wnt signaling pathway 6. inspiration of new routes for future treatment 7. conclusion

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Phosphatidic Acid Signals via the Hippo Pathway

Cited by 3 publications

References 10 publications

Spatiotemporal control of phosphatidic acid signaling with optogenetic, engineered phospholipase Ds

Spatiotemporal control of phosphatidic acid signaling with optogenetic, engineered phospholipase Ds

Regulation of Hippo Signaling by Mechanical Signals and the Cytoskeleton

YAP‑mediated crosstalk between the Wnt and Hippo signaling pathways (Review

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