Acinus integrates AKT1 and subapoptotic caspase activities to regulate basal autophagy.
Bottom Line: Acn stability also was regulated by AKT1-mediated phosphorylation.Physiologically, these flies showed improvements in processes known to be autophagy dependent, including increased starvation resistance, reduced Huntingtin-induced neurodegeneration, and prolonged life span.These data indicate that AKT1 and caspase-dependent regulation of Acn stability adjusts basal autophagy levels.
Affiliation: Department of Neuroscience and Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390.Show MeSH
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Mentions: To test which protease is responsible for cleaving Drosophila Acn, we performed a targeted RNAi screen. We took advantage of the rough eye phenotype resulting from eye-specific GMR-Gal4–driven expression of UAS-Acnwt at elevated temperature (28°C; Fig. 4, A and B). This phenotype was further enhanced when stabilized UAS-AcnD527A was expressed instead (Fig. 4 C). We reasoned that reduced activity of the protease responsible for Acn cleavage should enhance the roughness induced by UAS-Acnwt to a similar level to that of cleavage-resistant UAS-AcnD527A.
Affiliation: Department of Neuroscience and Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390.