Figure 7: Prdx4 oxidative activity blocks GDE2 trafficking. | Nature Communications

Figure 7: Prdx4 oxidative activity blocks GDE2 trafficking.

From: Prdx4 is a compartment-specific H2O2 sensor that regulates neurogenesis by controlling surface expression of GDE2

Figure 7

(a–c) Western blots of surface biotinylation assays in transfected HEK293T cells. These are representative of (a) n=7, (b) n=6, (c) n=5–7 different transfection experiments. (d–h) Live-cell staining of Prdx4 (green), GDE2 (FLAG, purple) and surface GDE2 (red) in transfected HEK293T cells. Panels represent one of 20 different areas imaged for each experiment. Arrows mark cells with surface GDE2 expression; asterisks (*) marks cells with very low surface GDE2 expression. Scale bar, 20 μm. (i) Schematic diagram of GDE2 showing epitope locations for FLAG and GDE2Loop antibodies utilized in d–h. (j) Model of Prdx4 inhibition of GDE2 function. Prdx4 monomers in the ER lumen are oxidized by H2O2 at their redox active C118 and C239 Cys to form dimers; these dimers subsequently oxidize Cys residues in the GDE2 GDPD domain, which inhibits GDE2 surface localization. When Prdx4 dimer levels decrease, the GDE2 GDPD domain escapes oxidation, and GDE2 traffics to the cell surface where it induces neurogenesis of neighbouring progenitors by GPI-anchor cleavage.

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