title: BDNF regulates Rab11-mediated recycling endosome dynamics to induce dendritic branching.
abstract: 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.
authors.affiliation: Neuronal Cell Biology and Regeneration Laboratory, Millennium Nucleus of Regenerative Biology, Center of Aging and Regeneration, Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago CP 8331010, Chile.
authors.forename: Oscar M
authors.initials: OM
authors.lastname: Lazo
authors.forename: Andrés
authors.initials: A
authors.lastname: Gonzalez
authors.forename: Maria
authors.initials: M
authors.lastname: Ascaño
authors.forename: Rejji
authors.initials: R
authors.lastname: Kuruvilla
authors.forename: Andrés
authors.initials: A
authors.lastname: Couve
authors.forename: Francisca C
authors.initials: FC
authors.lastname: Bronfman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D004622:Embryo, Mammalian; D004705:Endocytosis / Q000187:drug effects; D011992:Endosomes / Q000187:drug effects* / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D026121:Indole Alkaloids / Q000494:pharmacology; D008297:Male; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009218:Myosins / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D020813:Receptor, trkB / Q000378:metabolism; D053778:Thiazolidines / Q000494:pharmacology; D014162:Transfection
chemical_list: D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; C101826:Myo5b protein, rat; D034741:RNA, Small Interfering; D053778:Thiazolidines; C492252:Wdr44 protein, rat; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D006160:Guanosine Triphosphate; C049985:staurosporine aglycone; D020813:Receptor, trkB; D019204:GTP-Binding Proteins; D009218:Myosins; C037067:latrunculin A
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