Tep1 Regulates Yki Activity in Neural Stem Cells in Drosophila Glioma Model

Gangwani, Karishma; Snigdha, Kirti; Kango‐Singh, Madhuri

doi:10.3389/fcell.2020.00306

Cited by 8 publications

(8 citation statements)

References 59 publications

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“…Remarkably, concerted overexpression of ras and dilp-6 induced Dpn in potentially all glial cells and more, consistently with further Dpn+ cell proliferation. Consistent with our findings, ectopic neuroblasts were also observed upon co-expression of activated ras V12 and knock-down of PTEN in glia, within glioma models in Drosophila ( Gangwani et al, 2020 ). We demonstrated that ectopic Dpn+ originated from glia, most particularly neuropile glia (midline glia and ‘Drosophila astrocytes’).…”

Section: Discussionsupporting

confidence: 90%

Regenerative neurogenic response from glia requires insulin-driven neuron-glia communication

Harrison

Connolly

Gubieda

et al. 2021

eLife

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Understanding how injury to the Central Nervous System (CNS) induces de novo neurogenesis in animals would help promote regeneration in humans. Regenerative neurogenesis could originate from glia and glial Neuron-Glia antigen-2 (NG2) may sense injury-induced neuronal signals, but these are unknown. Here, we used Drosophila to search for genes functionally related the NG2 homologue kon-tiki (kon), and identified Islet Antigen-2 (Ia-2), required in neurons for insulin secretion. Alterations in Ia-2 function induced neural stem cell gene expression, injury increased ia-2 expression and induced ectopic neural stem cells. Using genetic analysis and lineage tracing, we demonstrate that Ia-2 and Kon regulate Drosophila insulin-like peptide 6 (Dilp-6), to induce glial proliferation and neural stem cells from glia. Ectopic neural stem cells can divide, and limited de novo neurogenesis could be traced back to glial cells. Altogether, Ia-2 and Dilp-6 drive a neuron-glia relay that restores glia, and reprograms glia into neural stem cells for regeneration.

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Section: Discussionsupporting

confidence: 90%

Regenerative neurogenic response from glia requires insulin-driven neuron-glia communication

Harrison

Connolly

Gubieda

et al. 2021

eLife

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“…They also found that suppression of CD109 downregulated the YAP/TAZ signature and decreased the TAZ protein level in glioma stem cells. Likewise, Gangwani et al reported that the Drosophila Tep1 gene (ortholog of human CD109) regulates Yki (the Drosophila ortholog of human YAP/TAZ) using a Drosophila glioma cell model [ 29 ]. However, the molecular mechanism through which CD109 regulates YAP/TAZ was not clarified in the abovementioned studies.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of CD109 Promotes the Epithelial-to-Mesenchymal Transition and Stemness Properties of Lung Adenocarcinomas via Activation of the Hippo-YAP Signaling

Lee

Kuo

Chou

et al. 2020

Cells

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Metastasis is the leading cause of death in lung adenocarcinomas. Identifying potential prognostic biomarkers and exploiting regulatory mechanisms could improve the diagnosis and treatment of lung cancer patients. We previously found that cluster of differentiation 109 (CD109) was upregulated in lung tumor tissues, and CD109 overexpression was correlated with the invasive and metastatic capacities of lung adenocarcinoma cells. However, the contribution of CD109 to lung tumorigenesis remains to be elucidated. In the present study, we identified that CD109 was upregulated in metastatic lung adenocarcinoma cells, and elevation of CD109 was correlated with epithelial-to-mesenchymal transition (EMT) traits in patients with lung adenocarcinoma. Functionally, CD109 expression was crucial for EMT gene expressions, tumor invasiveness, and cancer stemness properties. Moreover, elevation of CD109 was accompanied by upregulation of the yes-associated protein (YAP) signature in metastatic lung cancer cells and lung cancer patients, and activation of YAP was demonstrated to participate in CD109-elicited EMT gene expressions and tumor invasiveness. Our study reveals the molecular mechanism underlying CD109 in lung tumor aggressiveness, and CD109 could be a potential diagnostic and therapeutic target for lung cancer patients.

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“…Here, CD109 was suggested to act upstream of the Yap/Taz signaling pathway ( Minata et al, 2019 ). In a Drosophila glioma model, it was also shown that TEP1 ( Drosophila ortholog of human CD109) regulates the Drosophila Yki pathway (ortholog to Yap/Taz) ( Gangwani et al, 2020 ). This functional consensus of TEP1 and CD109 might also favor a structural similarity between both proteins.…”

Section: Discussionmentioning

confidence: 99%

Cell Surface Processing of CD109 by Meprin β Leads to the Release of Soluble Fragments and Reduced Expression on Extracellular Vesicles

Lückstädt¹,

Bub²,

Koudelka³

et al. 2021

Front. Cell Dev. Biol.

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Cluster of differentiation 109 (CD109) is a glycosylphosphatidylinositol (GPI)-anchored protein expressed on primitive hematopoietic stem cells, activated platelets, CD4+ and CD8+ T cells, and keratinocytes. In recent years, CD109 was also associated with different tumor entities and identified as a possible future diagnostic marker linked to reduced patient survival. Also, different cell signaling pathways were proposed as targets for CD109 interference including the TGFβ, JAK-STAT3, YAP/TAZ, and EGFR/AKT/mTOR pathways. Here, we identify the metalloproteinase meprin β to cleave CD109 at the cell surface and thereby induce the release of cleavage fragments of different size. Major cleavage was identified within the bait region of CD109 residing in the middle of the protein. To identify the structural localization of the bait region, homology modeling and single-particle analysis were applied, resulting in a molecular model of membrane-associated CD109, which allows for the localization of the newly identified cleavage sites for meprin β and the previously published cleavage sites for the metalloproteinase bone morphogenetic protein-1 (BMP-1). Full-length CD109 localized on extracellular vesicles (EVs) was also identified as a release mechanism, and we can show that proteolytic cleavage of CD109 at the cell surface reduces the amount of CD109 sorted to EVs. In summary, we identified meprin β as the first membrane-bound protease to cleave CD109 within the bait region, provide a first structural model for CD109, and show that cell surface proteolysis correlates negatively with CD109 released on EVs.

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Tep1 Regulates Yki Activity in Neural Stem Cells in Drosophila Glioma Model

Cited by 8 publications

References 59 publications

Regenerative neurogenic response from glia requires insulin-driven neuron-glia communication

Regenerative neurogenic response from glia requires insulin-driven neuron-glia communication

Upregulation of CD109 Promotes the Epithelial-to-Mesenchymal Transition and Stemness Properties of Lung Adenocarcinomas via Activation of the Hippo-YAP Signaling

Cell Surface Processing of CD109 by Meprin β Leads to the Release of Soluble Fragments and Reduced Expression on Extracellular Vesicles

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