Essential Role for Vav Guanine Nucleotide Exchange Factors in Brain-Derived Neurotrophic Factor-Induced Dendritic Spine Growth and Synapse Plasticity

Departments of Psychiatry and Ophthalmology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 08/2011; 31(35):12426-36. DOI: 10.1523/JNEUROSCI.0685-11.2011
Source: PubMed


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.

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    • "Additionally, BDNF regulates the trafficking and synaptic localization of PSD95 (Yoshii and Constantine-Paton, 2007), which is a major postsynaptic scaffolding protein that is sufficient to promote dendritic spine formation (El-Husseini et al., 2000). Furthermore, BDNF increases dendritic spine head width through mechanism that requires the Vav family of guanine nucleotide exchange factors (Hale et al., 2011). However, it is likely that additional downstream effectors mediate BDNF-induced dendritic spine formation and stability. "
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