The WD40-repeat proteins WDR-20 and WDR-48 bind and activate the deubiquitinating enzyme USP-46 to promote the abundance of the glutamate receptor GLR-1 in the ventral nerve cord of Caenorhabditis elegans

摘要: Ubiquitin-mediated endocytosis and degradation of glutamate receptors controls their synaptic abundance is implicated in modulating strength. The deubiquitinating enzymes (DUBs) that function the nervous system are beginning to be defined, but mechanisms control DUB activity vivo understood poorly. We found previously USP-46 deubiquitinates Caenorhabditis elegans receptor GLR-1 prevents its lysosome. WD40-repeat (WDR) proteins WDR20 WDR48/UAF1 have been shown bind USP46 stimulate catalytic other systems. Here we identify C. homologs these WDR show WDR-20 WDR-48 can vitro. Overexpression activator increases ventral nerve cord, this effect further enhanced by coexpression USP-46. Biochemical characterization indicates increase correlates with decreased levels ubiquitin-GLR-1 conjugates, suggesting WDR-20, WDR-48, together deubiquitinate stabilize neurons. results alterations locomotion behavior consistent increased glutamatergic signaling, blocked usp-46 loss-of-function mutants. Conversely, wdr-20 wdr-48 mutants exhibit changes signaling. propose form a complex vivo.