A Cullin1-Based SCF E3 Ubiquitin Ligase Targets the InR/PI3K/TOR Pathway to Regulate Neuronal Pruning

Pruning that selectively eliminates unnecessary axons/dendrites is crucial for sculpting the nervous system during development. during drosophila metamorphosis,dendrite arborization neurons,ddacs,selectively prune their larval dendrites in response to the steroid hormone ecdysone,whereas mushroom body γ neurons specifically eliminate their axon branches within dorsal and medial lobes. however,it is unknown which e3 ligase directs these two modes of pruning. here,we identified a conserved scf e3 ubiquitin ligase that plays a critical role in pruning of both ddac dendrites and mushroom body γ axons. the scf e3 ligase consists of four core components cullin1/roc1a/skpa/slimb and promotes ddac dendrite pruning downstream of ecr-b1 and sox14,but independently of mical. moreover,we demonstrate that the cullin1-based e3 ligase facilitates ddac dendrite pruning primarily through inactivation of the inr/pi3k/tor pathway. we show that the f-box protein slimb forms a complex with akt,an activator of the inr/pi3k/tor pathway,and promotes akt ubiquitination. activation of the inr/pi3k/tor pathway is sufficient to inhibit ddac dendrite pruning. thus,our findings provide a novel link between the e3 ligase and the inr/pi3k/tor pathway during dendrite pruning. © 2013 wong et al.