Dual regulation of dendritic morphogenesis in Drosophila by the COP9 signalosome.
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.
Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
Inna
I
Djagaeva
Sergey
S
Doronkin
D000818:Animals; D000075686:COP9 Signalosome Complex; D003433:Crosses, Genetic; D003712:Dendrites / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism*; D005786:Gene Expression Regulation; D007150:Immunohistochemistry / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008954:Models, Biological; D009024:Morphogenesis; D046912:Multiprotein Complexes / Q000378:metabolism* / Q000502:physiology*; D009154:Mutation; D000075687:NEDD8 Protein; D009474:Neurons / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism* / Q000502:physiology*; D010641:Phenotype; D014452:Ubiquitins / Q000378:metabolism
D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D000075687:NEDD8 Protein; C513173:Nedd8 protein, Drosophila; D014452:Ubiquitins; D010447:Peptide Hydrolases; C501491:CSN5 protein, Drosophila; D000075686:COP9 Signalosome Complex