Overexpression screen in Drosophila identifies neuronal roles of GSK-3 beta/shaggy as a regulator of AP-1-dependent developmental plasticity.
AP-1, an immediate-early transcription factor comprising heterodimers of the Fos and Jun proteins, has been shown in several animal models, including Drosophila, to control neuronal development and plasticity. In spite of this important role, very little is known about additional proteins that regulate, cooperate with, or are downstream targets of AP-1 in neurons. Here, we outline results from an overexpression/misexpression screen in Drosophila to identify potential regulators of AP-1 function at third instar larval neuromuscular junction (NMJ) synapses. First, we utilize >4000 enhancer and promoter (EP) and EPgy2 lines to screen a large subset of Drosophila genes for their ability to modify an AP-1-dependent eye-growth phenotype. Of 303 initially identified genes, we use a set of selection criteria to arrive at 25 prioritized genes from the resulting collection of putative interactors. Of these, perturbations in 13 genes result in synaptic phenotypes. Finally, we show that one candidate, the GSK-3beta-kinase homolog, shaggy, negatively influences AP-1-dependent synaptic growth, by modulating the Jun-N-terminal kinase pathway, and also regulates presynaptic neurotransmitter release at the larval neuromuscular junction. Other candidates identified in this screen provide a useful starting point to investigate genes that interact with AP-1 in vivo to regulate neuronal development and plasticity.
Franciscovich
A L
AL
Cell Biology Department, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Mortimer
A D Vrailas
AD
Freeman
A A
AA
Gu
J
J
Sanyal
S
S
D000818:Animals; D004330:Drosophila / Q000201:enzymology* / Q000235:genetics* / Q000254:growth & development; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007150:Immunohistochemistry; D007814:Larva / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D009474:Neurons / Q000201:enzymology* / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction; D009435:Synaptic Transmission / Q000235:genetics*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D018808:Transcription Factor AP-1; D000071679:Glycogen Synthase Kinase 3 beta; C080335:Sgg protein, Drosophila; D038362:Glycogen Synthase Kinase 3; D048670:MAP Kinase Kinase 4