Geranylgeranyltransferase I mediates BDNF-induced synaptogenesis
Geranylgeranyltransferase I mediates BDNF-induced synaptogenesis
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DOI：
10.1111/jnc.12249
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发表时间：
2013-06-01
影响因子：
4.7
通讯作者：
Zhou, Xiuping
中科院分区：
文献类型：
--
作者：
Li, Zhengwei;Sun, Chengdong;Zhou, Xiuping
香叶基香叶基转移酶I （Geranylgeranyltransferase I， GGT）是一种戊烯基转移酶，介导Rho小gtp酶的脂质修饰，如Rho、Rac和Cdc42，这些酶对神经元突触发生至关重要。虽然GGT在大脑中广泛表达，但GGT在中枢神经系统中的功能迄今仍不甚清楚。我们之前已经证明，GGT促进了培养海马神经元和小脑切片的基础和神经元活性以及脑源性神经营养因子（BDNF）诱导的树突形态发生。本研究旨在探讨GGT在神经元突触发生中的作用及其机制。我们发现，从P7到P28， GGT蛋白水平和活性在大鼠海马中逐渐升高，位于神经元突触的亚细胞。过表达GGT可增加Synapsin 1和突触后密度蛋白95的线密度，抑制或下调GGT可降低其线密度。此外，GGT及其已知底物Rac可被BDNF激活，从而促进培养海马神经元的突触发生。此外，bdnf诱导的突触发生被GGT抑制或下调以及非戊酰化的Rac1过表达所消除。综上所述，我们的数据表明GGT通过激活Rac1介导bdnf诱导的神经元突触发生。
Geranylgeranyltransferase I (GGT) is a prenyltransferase that mediates lipid modification of Rho small GTPases, such as Rho, Rac, and Cdc42, which are important for neuronal synaptogenesis. Although GGT is expressed in brain extensively, the function of GGT in central nerves system is largely unknown so far. We have previously demonstrated that GGT promotes the basal and neuronal activity and brain-derived neurotrophic factor (BDNF)-induced dendritic morphogenesis of cultured hippocampal neurons and cerebellar slices. This study is to explore the function and mechanism of GGT in neuronal synaptogenesis. We found that the protein level and activity of GGT gradually increased in rat hippocampus from P7 to P28 and subcellular located at synapse of neurons. The linear density of Synapsin 1 and post-synaptic density protein 95 increased by over-expression of GGT , while reduced by inhibition or down-regulation of GGT. In addition, GGT and its known substrate Rac was activated by BDNF, which promotes synaptogenesis in cultured hippocampal neurons. Furthermore, BDNF-induced synaptogenesis was eliminated by GGT inhibition or down-regulation, as well as by non-prenylated Rac1 over-expression. Together, our data suggested that GGT mediates BDNF-induced neuronal synaptogenesis through Rac1 activation.