dual regulation of dendritic morphogenesis in drosophila by the cop9 signalosome双重调节树突形态发生在果蝇cop9 signalosome.pdfVIP

Dual Regulation of Dendritic Morphogenesis in Drosophila by the COP9 Signalosome Inna Djagaeva, Sergey Doronkin* Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America Abstract Altered dendritic arborization contributes to numerous physiological processes including synaptic plasticity, behavior, learning and memory, and is one of the most consistent neuropathologic conditions found in a number of mental retardation disorders, schizophrenia, and neurodegenerative disease. COP9 signalosome (CSN), an evolutionarily conserved regulator of the Cullin-based ubiquitin ligases that act in the proteasome pathway, has been found associated with diverse debilitating syndromes, suggesting that CSN may be involved in regulation of dendritic arborization. However, the mechanism of this control, if it exists, is unknown. To address whether the CSN pathway plays a role in dendrites, we used a simple and genetically tractable model, Drosophila larval peripheral nervous system. Our model study identified the COP9 signalosome as the key and multilayer regulator of dendritic arborization. CSN is responsible for shaping the entire dendritic tree through both stimulating and then repressing dendritic branching. We identified that CSN exerts its dualistic function via control of different Cullins. In particular, CSN stimulates dendritic branching through Cullin1, and inhibits it via control of Cullin3 function. We also identified that Cullin1 acts in neurons with the substrate-specific F-box protein Slimb to target the Cubitus interruptus protein for degradation. Citation: Djagaeva I, Doronkin S (2009) Dual Regulation of Dendritic Morphogenesis in Drosophila by the COP9 Signalosome. PLoS ONE 4(10): e7577. doi:10.1371/ journal.pone.0007577 Editor: Patrick