Related Experiment Video
Updated: Aug 7, 2026

Evaluation of Synapse Density in Hippocampal Rodent Brain Slices
Published on: October 6, 2017
Highwire restrains synaptic growth by attenuating a MAP kinase signal
Catherine A Collins1, Yogesh P Wairkar, Sylvia L Johnson
1Department of Molecular Biology and Pharmacology, Washington University School of Medicine, Washington University, St. Louis, Missouri 63110, USA.
None:
Highwire is an extremely large, evolutionarily conserved E3 ubiquitin ligase that negatively regulates synaptic growth at the Drosophila NMJ. Highwire has been proposed to restrain synaptic growth by downregulating a synaptogenic signal. Here we identify such a downstream signaling pathway. A screen for suppressors of the highwire synaptic overgrowth phenotype yielded mutations in wallenda, a MAP kinase kinase kinase (MAPKKK) homologous to vertebrate DLK and LZK. wallenda is both necessary for highwire synaptic overgrowth and sufficient to promote synaptic overgrowth, and synaptic levels of Wallenda protein are controlled by Highwire and ubiquitin hydrolases. highwire synaptic overgrowth requires the MAP kinase JNK and the transcription factor Fos. These results suggest that Highwire controls structural plasticity of the synapse by regulating gene expression through a MAP kinase signaling pathway. In addition to controlling synaptic growth, Highwire promotes synaptic function through a separate pathway that does not require wallenda.
Related Concept Videos
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
MAPK Signaling Cascades
Microtubule Associated Proteins (MAPs)
The JAK-STAT Signaling Pathway
Amplifying Signals via Enzymatic Cascade
Calmodulin-dependent Signaling
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
