Essential role for vav guanine nucleotide exchange factors in brain-derived neurotrophic factor-induced dendritic spine growth and synapse plasticity

Carly F. Hale, Karen C. Dietz, Juan A. Varela, Cody B. Wood, Benjamin C. Zirlin, Leah S. Leverich, Robert W. Greene, Christopher W. Cowan

Research output: Contribution to journalArticle

36 Citations (Scopus)

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.Wefind 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.

Original languageEnglish (US)
Pages (from-to)12426-12436
Number of pages11
JournalJournal of Neuroscience
Volume31
Issue number35
DOIs
StatePublished - Aug 31 2011

Fingerprint

Proto-Oncogene Proteins c-vav
Dendritic Spines
Brain-Derived Neurotrophic Factor
Synapses
Growth
trkB Receptor
Guanine Nucleotide Exchange Factors
Neurons
Long-Term Potentiation
Guanosine Triphosphate
Actins
Hippocampus
Enzymes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Essential role for vav guanine nucleotide exchange factors in brain-derived neurotrophic factor-induced dendritic spine growth and synapse plasticity. / Hale, Carly F.; Dietz, Karen C.; Varela, Juan A.; Wood, Cody B.; Zirlin, Benjamin C.; Leverich, Leah S.; Greene, Robert W.; Cowan, Christopher W.

In: Journal of Neuroscience, Vol. 31, No. 35, 31.08.2011, p. 12426-12436.

Research output: Contribution to journalArticle

Hale, Carly F. ; Dietz, Karen C. ; Varela, Juan A. ; Wood, Cody B. ; Zirlin, Benjamin C. ; Leverich, Leah S. ; Greene, Robert W. ; Cowan, Christopher W. / Essential role for vav guanine nucleotide exchange factors in brain-derived neurotrophic factor-induced dendritic spine growth and synapse plasticity. In: Journal of Neuroscience. 2011 ; Vol. 31, No. 35. pp. 12426-12436.
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AU - Wood, Cody B.

AU - Zirlin, Benjamin C.

AU - Leverich, Leah S.

AU - Greene, Robert W.

AU - Cowan, Christopher W.

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