Biomaterial Database

Geranylgeranyltransferase I is essential for dendritic development of cerebellar Purkinje cells. 2010

Kong-Yan Wu, and Xiu-Ping Zhou, and Zhen-Ge Luo

Institute of Neuroscience, State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.

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.

UI	MeSH Term	Description	Entries
D009024	Morphogenesis	The development of anatomical structures to create the form of a single- or multi-cell organism. Morphogenesis provides form changes of a part, parts, or the whole organism.
D011689	Purkinje Cells	The output neurons of the cerebellar cortex.	Purkinje Cell,Purkinje Neuron,Purkyne Cell,Cell, Purkinje,Cell, Purkyne,Cells, Purkinje,Cells, Purkyne,Neuron, Purkinje,Neurons, Purkinje,Purkinje Neurons,Purkyne Cells
D003712	Dendrites	Extensions of the nerve cell body. They are short and branched and receive stimuli from other NEURONS.	Dendrite
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D019208	Brain-Derived Neurotrophic Factor	A member of the nerve growth factor family of trophic factors. In the brain BDNF has a trophic action on retinal, cholinergic, and dopaminergic neurons, and in the peripheral nervous system it acts on both motor and sensory neurons. (From Kendrew, The Encyclopedia of Molecular Biology, 1994)	BDNF,Brain Derived Neurotrophic Factor,Factor, Brain-Derived Neurotrophic,Neurotrophic Factor, Brain-Derived
D019883	Alkyl and Aryl Transferases	A somewhat heterogeneous class of enzymes that catalyze the transfer of alkyl or related groups (excluding methyl groups). EC 2.5.	Alkyltransferase,Alkyltransferases,Aryltransferase,Aryltransferases
D034741	RNA, Small Interfering	Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.	RNA, Scan,Repeat-Associated siRNA,Scan RNA,Small Scan RNA,Trans-Acting siRNA,siRNA,siRNA, Repeat-Associated,siRNA, Trans-Acting,Short Hairpin RNA,Short Interfering RNA,Small Hairpin RNA,Small Interfering RNA,scnRNA,shRNA,tasiRNA,Hairpin RNA, Short,Hairpin RNA, Small,Interfering RNA, Short,Interfering RNA, Small,RNA, Short Hairpin,RNA, Short Interfering,RNA, Small Hairpin,RNA, Small Scan,Repeat Associated siRNA,Scan RNA, Small,Trans Acting siRNA,siRNA, Repeat Associated,siRNA, Trans Acting