Geranylgeranyltransferase I mediates BDNF-induced synaptogenesis.

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 β, 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.