Autophagy promotes synapse development in Drosophila.
Autophagy, a lysosome-dependent degradation mechanism, mediates many biological processes, including cellular stress responses and neuroprotection. In this study, we demonstrate that autophagy positively regulates development of the Drosophila melanogaster larval neuromuscular junction (NMJ). Autophagy induces an NMJ overgrowth phenotype closely resembling that of highwire (hiw), an E3 ubiquitin ligase mutant. Moreover, like hiw, autophagy-induced NMJ overgrowth is suppressed by wallenda (wnd) and by a dominant-negative c-Jun NH(2)-terminal kinase (bsk(DN)). We show that autophagy promotes NMJ growth by reducing Hiw levels. Thus, autophagy and the ubiquitin-proteasome system converge in regulating synaptic development. Because autophagy is triggered in response to many environmental cues, our findings suggest that it is perfectly positioned to link environmental conditions with synaptic growth and plasticity.
Shen
Wei
W
Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA.
Ganetzky
Barry
B
D000588:Amines / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000235:genetics*; D004330:Drosophila / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000378:metabolism; D007150:Immunohistochemistry; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D007814:Larva / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D000588:Amines; D029721:Drosophila Proteins; D005456:Fluorescent Dyes; C409633:HIW protein, Drosophila; D009419:Nerve Tissue Proteins; C493330:Red DND-99; D006735:Horseradish Peroxidase; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; C512899:wnd protein, Drosophila; D016650:Fluorescein-5-isothiocyanate