Drosophila Rae1 controls the abundance of the ubiquitin ligase Highwire in post-mitotic neurons

Xiaolin Tian, Jing Li, Vera Valakh, Aaron Diantonio, Chunlai Wu

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

The evolutionarily conserved Highwire (Hiw)/Drosophila Fsn E3 ubiquitin ligase complex is required for normal synaptic morphology during development and axonal regeneration after injury. However, little is known about the molecular mechanisms that regulate the Hiw E3 ligase complex. Using tandem affinity purification techniques, we identified Drosophila Rae1 as a previously unknown component of the Hiw/Fsn complex. Loss of Rae1 function in neurons results in morphological defects at the neuromuscular junction that are similar to those seen in hiw mutants. We found that Rae1 physically and genetically interacts with Hiw and restrains synaptic terminal growth by regulating the MAP kinase kinase kinase Wallenda. Moreover, we found that the Rae1 is both necessary and sufficient to promote Hiw protein abundance, and it does so by binding to Hiw and protecting Hiw from autophagy-mediated degradation. These results describe a previously unknown mechanism that selectively controls Hiw protein abundance during synaptic development.

Original languageEnglish
Pages (from-to)1267-1275
Number of pages9
JournalNature neuroscience
Volume14
Issue number10
DOIs
StatePublished - Oct 2011

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