Regulation of protein prenyltransferase in central neurons

Abstract

Geranylgeranyltransferase I (GGT) is a protein prenyltransferase that mediates lipid modification of some proteins such as Rho family small GTPases. Since the activation of Rho GTPases mediates tumorgenesis and metastasis, GGT has become an attractive target for anti-tumor drug design. Although GGT is extensively expressed in the brain, the function of GGT in central nerves system (CNS) is totally unknown. We have previously shown that GGT was involved in neuromuscular synaptogenesis. In this study, we report that neuronal activity- and brain-derived neurotropic factor (BDNF)-dependent dendritic morphogenesis requires activation of GGT. Furthermore, GGT was activated by depolarization or BDNF in cultured neurons or in hippocampus of the mice under novelty exploration test, suggesting that neuronal activity activates GGT in vitro and in vivo. In this addendum, we further discuss the significance of this study and the possible implication to the field.

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Acknowledgements

This work was supported by National Natural Science Foundation of China (30721004, 30825013), Key State Research Program of China (2006CB806600 and 2006CB943900), Chinese Academy of Sciences Grant (KSCX2-YW-R-102), and Program of Shanghai Subject Chief Scientist (08XD14050).

Figures and Tables

Figure 1 KCl depolarization-induced GGT activation was blocked by K252a or TrkB/Fc. Neurons at DIV6 were pretreated with K252a or TrkB/Fc respectively for 45 min, then treated with KCl for another 45 min. After treatment, neurons were lysed and GGT activity was assayed by using Dansyl-GCVLL as substrate. Data shown are mean ± SEM of three independent experiments, with each performed in triplicate. All values were normalized to control neurons. *p < 0.05; ANOVA with Tukey test.

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