latrunculin-a and staurosporine-aglycone

Dendritic arborization of neurons is regulated by brain-derived neurotrophic factor (BDNF) together with its receptor, TrkB. Endocytosis is required for dendritic branching and regulates TrkB signaling, but how postendocytic trafficking determines the neuronal response to BDNF is not well understood. The monomeric GTPase Rab11 regulates the dynamics of recycling endosomes and local delivery of receptors to specific dendritic compartments. We investigated whether Rab11-dependent trafficking of TrkB in dendrites regulates BDNF-induced dendritic branching in rat hippocampal neurons. We report that TrkB in dendrites is a cargo for Rab11 endosomes and that both Rab11 and its effector, MyoVb, are required for BDNF/TrkB-induced dendritic branching. In addition, BDNF induces the accumulation of Rab11-positive endosomes and GTP-bound Rab11 in dendrites and the expression of a constitutively active mutant of Rab11 is sufficient to increase dendritic branching by increasing TrkB localization in dendrites and enhancing sensitization to endogenous BDNF. We propose that Rab11-dependent dendritic recycling provides a mechanism to retain TrkB in dendrites and to increase local signaling to regulate arborization.

Topics: Analysis of Variance; Animals; Antibodies; Brain-Derived Neurotrophic Factor; Bridged Bicyclo Compounds, Heterocyclic; Carbazoles; Cells, Cultured; Dendrites; Embryo, Mammalian; Endocytosis; Endosomes; Enzyme Inhibitors; Female; Gene Expression Regulation; Green Fluorescent Proteins; GTP-Binding Proteins; Guanosine Triphosphate; Hippocampus; Indole Alkaloids; Male; Microscopy, Confocal; Microtubule-Associated Proteins; Mutation; Myosins; Neurons; Rats; Receptor, trkB; RNA, Small Interfering; Thiazolidines; Transfection