Protein O-GlcNAcylation Is Required for Fibroblast Growth Factor Signaling in
            <i>Drosophila</i>

Mariappa, Daniel; Sauert, Kathrin; Mariño, Karina; Turnock, Daniel C.; Webster, Ryan; Aalten, Daan M. F. van; Ferguson, Michael A. J.; Müller, H.‐Arno J.

doi:10.1126/scisignal.2002335

Cited by 24 publications

(17 citation statements)

References 38 publications

(56 reference statements)

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“…The transition from naïve to primed state is mediated by the actions of the Erk1/2 kinases downstream of fibroblast growth factor (Fgf) signaling. Recent work in Drosophila has identified a requirement for O ‐GlcNAcylation for Erk1/2 signal transduction downstream of Fgf receptor . However, consistent with a normal transition to the primed state, we did not detect any changes in the profile of Erk1/2 phosphorylation in GNS‐treated cells (Supporting Information Fig.…”

Section: Resultssupporting

confidence: 76%

Elevated O-GlcNAc Levels Activate Epigenetically Repressed Genes and Delay Mouse ESC Differentiation Without Affecting Naïve to Primed Cell Transition

et al. 2014

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The differentiation of mouse embryonic stem cells (ESCs) is controlled by the interaction of multiple signaling pathways, typically mediated by post‐translational protein modifications. The addition of O‐linked N‐acetylglucosamine (O‐GlcNAc) to serine and threonine residues of nuclear and cytoplasmic proteins is one such modification (O‐GlcNAcylation), whose function in ESCs is only now beginning to be elucidated. Here, we demonstrate that the specific inhibition of O‐GlcNAc hydrolase (Oga) causes increased levels of protein O‐GlcNAcylation and impairs differentiation of mouse ESCs both in serum‐free monolayer and in embryoid bodies (EBs). Use of reporter cell lines demonstrates that Oga inhibition leads to a reduction in the number of Sox1‐expressing neural progenitors generated following induction of neural differentiation as well as maintained expression of the ESC marker Oct4 (Pou5f1). In EBs, expression of mesodermal and endodermal markers is also delayed. However, the transition of naïve cells to primed pluripotency indicated by Rex1 (Zfp42), Nanog, Esrrb, and Dppa3 downregulation and Fgf5 upregulation remains unchanged. Finally, we demonstrate that increased O‐GlcNAcylation results in upregulation of genes normally epigenetically silenced in ESCs, supporting the emerging role for this protein modification in the regulation of histone modifications and DNA methylation. Stem Cells 2014;32:2605–2615

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Section: Resultssupporting

confidence: 76%

Elevated O-GlcNAc Levels Activate Epigenetically Repressed Genes and Delay Mouse ESC Differentiation Without Affecting Naïve to Primed Cell Transition

et al. 2014

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“…Different studies had already shown the importance of glycidic residues on proteins, mainly on the arthropod larval development. Mariappa et al (2011) showed the significance of the O-linked residues b-N-acetylglucosamine on the proteins of the embryos' mesoderm for the larval development and growth of Drosophila sp. For spider venom proteins, the process of glycosylation can be imperative for their activity and for the venom to exert its biological function (Veiga et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Brown spider (Loxosceles intermedia) hemolymph: Cellular and biochemical analyses

Bednaski

Trevisan-Silva

Matsubara

et al. 2015

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This is the first study on the hemolymph from a spider of the Loxosceles genus. These animals are responsible for a great number of envenomation cases worldwide. Several studies on Loxosceles venoms have been published, and the knowledge about the venom and its toxins is considerable, not only regarding the biological and biochemical characterization, but also regarding structural, genetic and phylogenetic approaches. However, the literature on Loxosceles hemolymph is nonexistent. The main goal of the present study was to characterize biochemically the hemolymph content, and especially, to identify its different hemocytes. Moreover, many papers have already shown molecules whose source is the hemolymph and their very interesting activities and biomedical applications, for example, antifungal and antibacterial activities. A 2D-SDS-PAGE of brown spider hemolymph showed approximately 111 spots for pH 3-10 and 150 spots for pH 4-7. A lectin-blotting assay showed that hemolymph carbohydrate residues were similar to those found in venom. Several types of TAG and DAG phospholipids were found in the hemolymph and characterized by HPTLC and mass spectrometry. Four different hemocytes were characterized in Loxosceles intermedia hemolymph: prohemocyte, plasmatocyte, granulocyte and adipohemocyte. This paper opens new possibilities on toxinology, studying an unknown biological material, and it characterizes a source of molecules with putative biotechnological applications.

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“…Whether Dof is involved in determining the specificity of FGF responses in the cell or merely acts as a modular scaffold protein is currently unclear. Recently, it was shown that cytosolic UDP-N-Acetylglucosamine (UDP-GlcNAc) levels are important for FGF signalling in Drosophila and that UDP-GlcNAc is required downstream of the receptor at the level of Dof [66]. Dof was shown to be O -GlcNAcylated in an O -GlcNAc Transferase dependent fashion indicating that posttranslational protein O -GlcNAcylation of Dof is required for its function in the pathway.…”

Section: The Fgf Signalling Pathway In Drosophilamentioning

confidence: 99%

Functions and Mechanisms of Fibroblast Growth Factor (FGF) Signalling in Drosophila melanogaster

Muha

Müller

2013

IJMS

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Intercellular signalling via growth factors plays an important role in controlling cell differentiation and cell movements during the development of multicellular animals. Fibroblast Growth Factor (FGF) signalling induces changes in cellular behaviour allowing cells in the embryo to move, to survive, to divide or to differentiate. Several examples argue that FGF signalling is used in multi-step morphogenetic processes to achieve and maintain a transitional state of the cells required for the control of cell fate. In the genetic model Drosophila melanogaster, FGF signalling via the receptor tyrosine kinases Heartless (Htl) and Breathless (Btl) is particularly well studied. These FGF receptors affect gene expression, cell shape and cell–cell interactions during mesoderm layer formation, caudal visceral muscle (CVM) formation, tracheal morphogenesis and glia differentiation. Here, we will address the current knowledge of the biological functions of FGF signalling in the fly on the tissue, at a cellular and molecular level.

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Protein O-GlcNAcylation Is Required for Fibroblast Growth Factor Signaling in Drosophila

Cited by 24 publications

References 38 publications

Elevated O-GlcNAc Levels Activate Epigenetically Repressed Genes and Delay Mouse ESC Differentiation Without Affecting Naïve to Primed Cell Transition

Elevated O-GlcNAc Levels Activate Epigenetically Repressed Genes and Delay Mouse ESC Differentiation Without Affecting Naïve to Primed Cell Transition

Characterization of Brown spider (Loxosceles intermedia) hemolymph: Cellular and biochemical analyses

Functions and Mechanisms of Fibroblast Growth Factor (FGF) Signalling in Drosophila melanogaster

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