Regulatory role of Wdr24 in autophagy activity during zebrafish embryogenesis
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TOR and autophagy are essential pathways to mediate anabolic and catabolic reactions, respectively, in response to various nutritional stimuli. Vertebrate development requires such reactions to achieve the common goal of generating an independent organism from a single fertilized egg.
Using the zebrafish as an animal model, we characterized the role of Wdr24, a component of the GATOR2 complex that reportedly activates TORC1.
Sequence analysis and subcellular localization of zebrafish Wdr24 suggested functional resemblance to its mammalian counterpart. We found that wdr24 expression commences during early embryogenesis, implicating its requirement. Accordingly, wdr24 knockdown induced defective embryogenesis accompanied by massive cell death. The developmental defects induced by wdr24 knockdown were attributable, at least in part, to dysregulated autophagy, which could be partially restored by wdr24 overexpression.
These findings suggest that a conserved role of Wdr24 may be a critical part of the cellular metabolism in different species.
KeywordsWdr24 GATOR2 TORC1 Autophagy Zebrafish
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