Synaptic and genomic responses to JNK and AP-1 signaling in Drosophila neurons.
BACKGROUND
The transcription factor AP-1 positively controls synaptic plasticity at the Drosophila neuromuscular junction. Although in motor neurons, JNK has been shown to activate AP-1, a positive regulator of growth and strength at the larval NMJ, the consequences of JNK activation are poorly studied. In addition, the downstream transcriptional targets of JNK and AP-1 signaling in the Drosophila nervous system have yet to be identified. Here, we further investigated the role of JNK signaling at this model synapse employing an activated form of JNK-kinase; and using Serial Analysis of Gene Expression and oligonucleotide microarrays, searched for candidate early targets of JNK or AP-1 dependent transcription in neurons.


RESULTS
Temporally-controlled JNK induction in postembryonic motor neurons triggers synaptic growth at the NMJ indicating a role in developmental plasticity rather than synaptogenesis. An unexpected observation that JNK activation also causes a reduction in transmitter release is inconsistent with JNK functioning solely through AP-1 and suggests an additional, yet-unidentified pathway for JNK signaling in motor neurons. SAGE profiling of mRNA expression helps define the neural transcriptome in Drosophila. Though many putative AP-1 and JNK target genes arose from the genomic screens, few were confirmed in subsequent validation experiments. One potentially important neuronal AP-1 target discovered, CG6044, was previously implicated in olfactory associative memory. In addition, 5 mRNAs regulated by RU486, a steroid used to trigger conditional gene expression were identified.


CONCLUSIONS
This study demonstrates a novel role for JNK signaling at the larval neuromuscular junction and provides a quantitative profile of gene transcription in Drosophila neurons. While identifying potential JNK/AP-1 targets it reveals the limitations of genome-wide analyses using complex tissues like the whole brain.
Etter
Paul D
PD
Department of Molecular & Cellular Biology, University of Arizona, Tucson, USA. pdetter@u.arizona.edu
Narayanan
Radhakrishnan
R
Navratilova
Zaneta
Z
Patel
Chirag
C
Bohmann
Dirk
D
Jasper
Heinrich
H
Ramaswami
Mani
M
D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D023281:Genomics / Q000379:methods*; D048670:MAP Kinase Kinase 4 / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D009474:Neurons / Q000502:physiology; D040081:Protein Array Analysis / Q000379:methods; D015398:Signal Transduction / Q000235:genetics*; D013569:Synapses / Q000235:genetics* / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000096:biosynthesis / Q000235:genetics*
D029721:Drosophila Proteins; D018808:Transcription Factor AP-1; D048670:MAP Kinase Kinase 4