Highwire Restrains Synaptic Growth by Attenuating a MAP Kinase Signal

Catherine A. Collins, Yogesh Wairkar, Sylvia L. Johnson, Aaron DiAntonio

Research output: Contribution to journalArticle

221 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)57-69
Number of pages13
JournalNeuron
Volume51
Issue number1
DOIs
StatePublished - Jul 6 2006
Externally publishedYes

Fingerprint

Phosphotransferases
Growth
MAP Kinase Kinase 4
MAP Kinase Kinase Kinases
Ubiquitin-Protein Ligases
MAP Kinase Signaling System
Hydrolases
Ubiquitin
Synapses
Drosophila
Vertebrates
Transcription Factors
Down-Regulation
Phenotype
Gene Expression
Mutation
Proteins

Keywords

  • DEVBIO
  • MOLNEURO
  • SIGNALING

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Highwire Restrains Synaptic Growth by Attenuating a MAP Kinase Signal. / Collins, Catherine A.; Wairkar, Yogesh; Johnson, Sylvia L.; DiAntonio, Aaron.

In: Neuron, Vol. 51, No. 1, 06.07.2006, p. 57-69.

Research output: Contribution to journalArticle

Collins, Catherine A. ; Wairkar, Yogesh ; Johnson, Sylvia L. ; DiAntonio, Aaron. / Highwire Restrains Synaptic Growth by Attenuating a MAP Kinase Signal. In: Neuron. 2006 ; Vol. 51, No. 1. pp. 57-69.
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