Drosophila alicorn is a neuronal maintenance factor protecting against activity-induced retinal degeneration.
Exploring mechanisms that govern neuronal responses to metabolic stress is essential for the development of therapeutic strategies aimed at treatment of neuronal injury and disease. AMP-activated protein kinase (AMPK) is a key enzyme regulating cellular energy homeostasis that responds to changes in cellular energy levels by promoting energy-restorative and inhibiting energy-consumptive processes. Recent studies have suggested that AMPK might have a neuroprotective function. However, the existing evidence is contradictory and almost exclusively derived from in vitro studies based on drug treatments and metabolic stress models. To tackle these issues in vivo, we used the Drosophila visual system. In this report, we describe a novel Drosophila mutant, alicorn (alc), encoding the single beta regulatory subunit of AMPK. Loss of alc using the eyFlp system causes severe early-onset progressive nonapoptotic neurodegeneration in the retina, the optic lobe, and the antennae, as well as behavioral and neurophysiological defects. Retinal degeneration occurs immediately after normal neuronal differentiation, can be enhanced by exposure to light, and can be prevented by blocking photoreceptor excitation. Furthermore, AMPK is required for proper viability of differentiated photoreceptors by mechanisms unrelated to polarity events that AMPK controls in epithelial tissues. In conclusion, AMPK does not affect photoreceptor development but is crucial to maintaining integrity of mature neurons under conditions of increased activity and provides protection from excitotoxicity.
Spasić
Milos R
MR
Laboratory of Developmental Genetics, Flanders Institute for Biotechnology (VIB), Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
Callaerts
Patrick
P
Norga
Koenraad K
KK
D055372:AMP-Activated Protein Kinases; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D004330:Drosophila; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005260:Female; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012162:Retinal Degeneration / Q000201:enzymology* / Q000235:genetics / Q000517:prevention & control*
D029721:Drosophila Proteins; D009097:Multienzyme Complexes; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases