Essential role for vav Guanine nucleotide exchange factors in brain-derived neurotrophic factor-induced dendritic spine growth and synapse plasticity.
Essential role for vav Guanine nucleotide exchange factors in brain-derived neurotrophic factor-induced dendritic spine growth and synapse plasticity.
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VAV鸟嘌呤核苷酸交换因子在脑源性神经营养因子诱导的树突状脊柱生长和突触可塑性中的重要作用。
DOI：
10.1523/jneurosci.0685-11.2011
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发表时间：
2011-08-31
期刊：
影响因子：
--
通讯作者：
Cowan CW
中科院分区：
文献类型：
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作者：
Hale CF;Dietz KC;Varela JA;Wood CB;Zirlin BC;Leverich LS;Greene RW;Cowan CW
脑源性神经营养因子 (BDNF) 及其同源受体 TrkB 调节广泛的细胞过程，包括树突棘形成和功能性突触可塑性。然而，将 BDNF 激活的 TrkB 与 F-肌动蛋白重塑酶和树突棘形态可塑性联系起来的信号机制仍知之甚少。我们在此报告，神经元中的 BDNF/TrkB 信号传导通过一种新的 TrkB 激酶依赖性机制激活 Rac/RhoA 鸟嘌呤核苷酸交换因子 (GEF) 的 Vav 家族。我们发现 Vav 是 BDNF 刺激皮质和海马神经元 Rac-GTP 产生所必需的。 Vav 在出生后海马的兴奋性突触处部分富集，但似乎不是正常树突棘密度所必需的。相反，我们观察到Vav缺陷的小鼠海马切片中BDNF诱导的快速树突棘头部生长和CA3-CA1 theta爆发刺激（TBS）长时程增强（LTP）显着减少，这表明树突棘形态可塑性的Vav依赖性调节有利于正常的功能性突触可塑性。
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 (GEFs) through a novel TrkB kinase-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 (TBS) long-term potentiation (LTP) in Vav-deficient mouse hippocampal slices, suggesting that Vav-dependent regulation of dendritic spine morphological plasticity facilitates normal functional synapse plasticity.