Geranylgeranyltransferase I is essential for dendritic development of cerebellar Purkinje cells.
BACKGROUND
During cerebellar development, Purkinje cells (PCs) form the most elaborate dendritic trees among neurons in the brain, but the mechanism regulating PC arborization remains largely unknown. Geranylgeranyltransferase I (GGT) is a prenyltransferase that is responsible for lipid modification of several signaling proteins, such as Rho family small GTPase Rac1, which has been shown to be involved in neuronal morphogenesis. Here we show that GGT plays an important role in dendritic development of PCs.


RESULTS
We found that GGT was abundantly expressed in the developing rat cerebellum, in particular molecular layer (ML), the region enriched with PC dendrites. Inhibition or down-regulation of GGT using small interference RNA (siRNA) inhibited dendritic development of PCs. In contrast, up-regulation of GGT promoted dendritic arborization of PCs. Furthermore, neuronal depolarization induced by high K+ or treatment with brain-derived neurotrophic factor (BDNF) promoted membrane association of Rac1 and dendritic development of PCs in cultured cerebellar slices. The effect of BDNF or high K+ was inhibited by inhibition or down-regulation of GGT.


CONCLUSIONS
Our results indicate that GGT plays an important role in Purkinje cell development, and suggest a novel role of GGT in neuronal morphogenesis in vivo.
Wu
Kong-Yan
KY
Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Zhou
Xiu-Ping
XP
Luo
Zhen-Ge
ZG
D019883:Alkyl and Aryl Transferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003712:Dendrites / Q000201:enzymology* / Q000502:physiology* / Q000648:ultrastructure; D009024:Morphogenesis / Q000502:physiology; D011689:Purkinje Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats
D019208:Brain-Derived Neurotrophic Factor; D034741:RNA, Small Interfering; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I