AMPK supports growth in Drosophila by regulating muscle activity and nutrient uptake in the gut.
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.
Bland
Michelle L
ML
Department of Medicine, Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania, Philadelphia, PA 19104, USA.
Lee
Robert J
RJ
Magallanes
Julie M
JM
Foskett
J Kevin
JK
Birnbaum
Morris J
MJ
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D003433:Crosses, Genetic; D004331:Drosophila melanogaster / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005947:Glucose / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000196:embryology; D008954:Models, Biological; D009130:Muscle, Smooth / Q000378:metabolism; D009132:Muscles / Q000196:embryology / Q000378:metabolism*; D010528:Peristalsis; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019076:Transgenes; D014280:Triglycerides / Q000378:metabolism
D014280:Triglycerides; D055372:AMP-Activated Protein Kinases; D005947:Glucose