Synaptic and genomic responses to JNK and AP-1 signaling in Drosophila neurons

BMC Neurosci. 2005 Jun 2;6:39. doi: 10.1186/1471-2202-6-39.

Abstract

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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Drosophila
  • Drosophila Proteins / biosynthesis
  • Drosophila Proteins / genetics*
  • Female
  • Genomics / methods*
  • MAP Kinase Kinase 4 / biosynthesis
  • MAP Kinase Kinase 4 / genetics*
  • Male
  • Neurons / physiology
  • Protein Array Analysis / methods
  • Signal Transduction / genetics*
  • Synapses / genetics*
  • Synapses / metabolism
  • Transcription Factor AP-1 / biosynthesis
  • Transcription Factor AP-1 / genetics*

Substances

  • Drosophila Proteins
  • Transcription Factor AP-1
  • MAP Kinase Kinase 4