AMPK supports growth in Drosophila by regulating muscle activity and nutrient uptake in the gut

Department of Medicine, Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania, Philadelphia, PA 19104, USA.
Developmental Biology (Impact Factor: 3.55). 08/2010; 344(1):293-303. DOI: 10.1016/j.ydbio.2010.05.010
Source: PubMed


The larval phase of the Drosophila life cycle is characterized by constant food intake, resulting in a two hundred-fold increase in mass over four days. Here we show that the conserved energy sensor AMPK is essential for nutrient intake in Drosophila. Mutants lacking dAMPKalpha are small, with low triglyceride levels, small fat body cells and early pupal lethality. Using mosaic analysis, we find that dAMPKalpha functions as a nonautonomous regulator of cell growth. Nutrient absorption is impaired in dAMPKalpha mutants, and this defect stems not from altered gut epithelial cell polarity but from impaired peristaltic activity. Expression of a wild-type dAMPKalpha transgene or an activated version of the AMPK target myosin regulatory light chain (MRLC) in the dAMPKalpha mutant visceral musculature restores gut function and growth. These data suggest strongly that AMPK regulates visceral smooth muscle function through phosphorylation of MRLC. Furthermore, our data show that in Drosophila, AMPK performs an essential cell-nonautonomous function, serving the needs of the organism by promoting activity of the visceral musculature and, consequently, nutrient intake.

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    • "The AMPK pathway senses energy levels in the cell by responding to intracellular adenosine nucleotide levels to regulate growth and metabolism in Drosophila larvae (Braco et al., 2012; Mihaylova and Shaw, 2012). In Drosophila larvae, blocking AMPK signaling appears to regulate growth by affecting contraction of the visceral muscle, thereby interfering with gut function (Bland et al., 2010). In mammals, AMPK signaling interacts with IIS/TOR by regulating TSC1/2 (Mihaylova and Shaw, 2012). "
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    • "ampkα mutants grown under energy stress have defects in apical/basal epithelial cell polarity in follicle cells within the ovary (Mirouse et al., 2007). In contrast, AMPKα mutants grown on nutrient rich food still show defects in embryonic epithelial polarity (Lee et al., 2007), neuroblast apical polarity (this work), and visceral muscle contraction (Bland et al., 2010). Larval neuroblasts, embryonic ectoderm, and visceral muscle may have a high metabolic rate, require low basal AMPK activity, or use a different mechanism to activate AMPK than epithelial cells. "
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    ABSTRACT: Drosophila neuroblasts are a model system for studying stem cell self-renewal and the establishment of cortical polarity. Larval neuroblasts generate a large apical self-renewing neuroblast, and a small basal cell that differentiates. We performed a genetic screen to identify regulators of neuroblast self-renewal, and identified a mutation in sgt1 (suppressor-of-G2-allele-of-skp1) that had fewer neuroblasts. We found that sgt1 neuroblasts have two polarity phenotypes: failure to establish apical cortical polarity at prophase, and lack of cortical Scribble localization throughout the cell cycle. Apical cortical polarity was partially restored at metaphase by a microtubule-induced cortical polarity pathway. Double mutants lacking Sgt1 and Pins (a microtubule-induced polarity pathway component) resulted in neuroblasts without detectable cortical polarity and formation of "neuroblast tumors." Mutants in hsp83 (encoding the predicted Sgt1-binding protein Hsp90), LKB1, or AMPKα all show similar prophase apical cortical polarity defects (but no Scribble phenotype), and activated AMPKα rescued the sgt1 mutant phenotype. We propose that an Sgt1/Hsp90-LKB1-AMPK pathway acts redundantly with a microtubule-induced polarity pathway to generate neuroblast cortical polarity, and the absence of neuroblast cortical polarity can produce neuroblast tumors.
    Preview · Article · Mar 2012 · Developmental Biology
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    • "AMPK may participate in this specialized population of cells to regulate AKH signaling, as well as in other potential cells including insulin [42], which is known to participate in the endocrine events that shape behavioral and physiological responses to starvation. During preparation of this manuscript, two independent reports showed similar phenotypes stemming from reduced AMPK function [36], [43]. One report showed a similar sensitivity to starvation conditions as we have, in Drosophila with reduced AMPK function through selective introduction of an RNAi element targeting the alpha subunit. "
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