title: Essential role for vav Guanine nucleotide exchange factors in brain-derived neurotrophic factor-induced dendritic spine growth and synapse plasticity.
abstract: Brain-derived neurotrophic factor (BDNF) and its cognate receptor, TrkB, regulate a wide range of cellular processes, including dendritic spine formation and functional synapse plasticity. However, the signaling mechanisms that link BDNF-activated TrkB to F-actin remodeling enzymes and dendritic spine morphological plasticity remain poorly understood. We report here that BDNF/TrkB signaling in neurons activates the Vav family of Rac/RhoA guanine nucleotide exchange factors through a novel TrkB-dependent mechanism. We find that Vav is required for BDNF-stimulated Rac-GTP production in cortical and hippocampal neurons. Vav is partially enriched at excitatory synapses in the postnatal hippocampus but does not appear to be required for normal dendritic spine density. Rather, we observe significant reductions in both BDNF-induced, rapid, dendritic spine head growth and in CA3-CA1 theta burst-stimulated long-term potentiation in Vav-deficient mouse hippocampal slices, suggesting that Vav-dependent regulation of dendritic spine morphological plasticity facilitates normal functional synapse plasticity.
authors: Departments of Psychiatry and Ophthalmology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors: Carly F
authors: CF
authors: Hale
authors: Karen C
authors: KC
authors: Dietz
authors: Juan A
authors: JA
authors: Varela
authors: Cody B
authors: CB
authors: Wood
authors: Benjamin C
authors: BC
authors: Zirlin
authors: Leah S
authors: LS
authors: Leverich
authors: Robert W
authors: RW
authors: Greene
authors: Christopher W
authors: CW
authors: Cowan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D049229:Dendritic Spines / Q000187:drug effects*; D004558:Electric Stimulation; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics; D051379:Mice; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000166:cytology* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism*; D051381:Rats; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D013574:Synaptosomes / Q000187:drug effects; D014162:Transfection / Q000379:methods
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D051567:Proto-Oncogene Proteins c-vav; D049452:Green Fluorescent Proteins