title: Developmental shaping of dendritic arbors in Drosophila relies on tightly regulated intra-neuronal activity of protein kinase A (PKA).
abstract: Dendrites develop morphologies characterized by multiple levels of complexity that involve neuron type specific dendritic length and particular spatial distribution. How this is developmentally regulated and in particular which signaling molecules are crucial in the process is still not understood. Using Drosophila class IV dendritic arborization (da) neurons we test in vivo the effects of cell-autonomous dose-dependent changes in the activity levels of the cAMP-dependent Protein Kinase A (PKA) on the formation of complex dendritic arbors. We find that genetic manipulations of the PKA activity levels affect profoundly the arbor complexity with strongest impact on distal branches. Both decreasing and increasing PKA activity result in a reduced complexity of the arbors, as reflected in decreased dendritic length and number of branching points, suggesting an inverted U-shape response to PKA. The phenotypes are accompanied by changes in organelle distribution: Golgi outposts and early endosomes in distal dendritic branches are reduced in PKA mutants. By using Rab5 dominant negative we find that PKA interacts genetically with the early endosomal pathway. We test if the possible relationship between PKA and organelles may be the result of phosphorylation of the microtubule motor dynein components or Rab5. We find that Drosophila cytoplasmic dynein components are direct PKA phosphorylation targets in vitro, but not in vivo, thus pointing to a different putative in vivo target. Our data argue that tightly controlled dose-dependent intra-neuronal PKA activity levels are critical in determining the dendritic arbor complexity, one of the possible ways being through the regulation of organelle distribution.
authors.affiliation: Department of Physiology and Cellular Biophysics, Columbia University Medical Center, 630 W. 168th St. P&S 12-403, NY 10032, USA; Institute of Molecular Biology and Biotechnology, Nikolaou Plastira 100, P.O Box 1385, GR-70013 Heraklion, Crete, Greece. Electronic address: ticopf@gmail.com.
authors.forename: Tijana
authors.initials: T
authors.lastname: Copf
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics*; D003712:Dendrites / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics; D004398:Dyneins / Q000378:metabolism; D011992:Endosomes / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006056:Golgi Apparatus / Q000502:physiology; D008870:Microtubules / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors; D020696:rab5 GTP-Binding Proteins / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; C557617:GAL4 protein, Drosophila; D014157:Transcription Factors; C084727:tub protein, Drosophila; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C586289:Rab5 protein, Drosophila; D004398:Dyneins; D020696:rab5 GTP-Binding Proteins
keywords: Complex arbor; Dendrites; Drosophila; Early endosomes; Golgi outposts; PKA