Objective Geranylgeranyltransferase Ⅰ (GGT Ⅰ) is a prenyltransferase that mediates lipid modification of Rho small GTPases such as Rho, Rac, Cdc42.Due to the high mutation rate of Rho small GTPases in many cancers, research about GGTI almost focuses on its role in cancers.Although GGTI expressed in brain extensively, the function of GGTI in central nerves system is not studied so far.We have previously demonstrated that GGTI can promote the basal and neuronal activity and brain-derived neurotrophic factor (BDNF)-indueed dendritic morphogenesis of cultured hippocampal neurons and cerebellar slices.The present study is to explore the function and mechanism of GGTI in neuronal synaptogenesis.Methods The GGTI protein level and location was examined by syanptosome or PSD fraetionation and Western blotting.The density of the presynaptic marker synapsin Ⅰ and the postsynaptic marker PSD95 were measured in cultured hippocampal neurons after transfection and immunofluoresence and confocal microscopy.The interaction between GGTI and tropomyosin-related kinase B (TrkB), the receptor for BDNF was identified by co-immunoprecipition assay and glutathione S-transferase (GST) pull-down assay.The active Rac was tested also by GST pull-down assay.Results We found that GGTI specific beta subunit protein level was gradually increased in rat hippocampus from P7 to P28, a period that is known to be important for the synaptogenesis in vivo and GGTI protein was enriched in synaptosome and postsynaptic fractions from P14 hippocampus.The linear density of synapsin Ⅰ and PSD95 were increased by over-expression of GGTI beta subunit, and reduced by inhibition or down-regulation of GGTI beta subunit.Furthermore, GGTI and its main substrate Rac was activated by BDNF, which promote synaptogenesis in cultured hippocampal neurons.Interestingly, GGTI was physically associated with TrkB.Conclusion Taken together, our preliminary data suggested that GGTI mediates BDNF-induced neuronal synaptogenesis through Rac activation.