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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 modificatio...

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Autores principales: Wu, Kong-Yan, Zhou, Xiu-Ping, Luo, Zhen-Ge
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902468/
https://www.ncbi.nlm.nih.gov/pubmed/20540740
http://dx.doi.org/10.1186/1756-6606-3-18
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author Wu, Kong-Yan
Zhou, Xiu-Ping
Luo, Zhen-Ge
author_facet Wu, Kong-Yan
Zhou, Xiu-Ping
Luo, Zhen-Ge
author_sort Wu, Kong-Yan
collection PubMed
description 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. CONCLUSION: 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.
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spelling pubmed-29024682010-07-13 Geranylgeranyltransferase I is essential for dendritic development of cerebellar Purkinje cells Wu, Kong-Yan Zhou, Xiu-Ping Luo, Zhen-Ge Mol Brain Research 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. CONCLUSION: 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. BioMed Central 2010-06-11 /pmc/articles/PMC2902468/ /pubmed/20540740 http://dx.doi.org/10.1186/1756-6606-3-18 Text en Copyright ©2010 Wu et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Wu, Kong-Yan
Zhou, Xiu-Ping
Luo, Zhen-Ge
Geranylgeranyltransferase I is essential for dendritic development of cerebellar Purkinje cells
title Geranylgeranyltransferase I is essential for dendritic development of cerebellar Purkinje cells
title_full Geranylgeranyltransferase I is essential for dendritic development of cerebellar Purkinje cells
title_fullStr Geranylgeranyltransferase I is essential for dendritic development of cerebellar Purkinje cells
title_full_unstemmed Geranylgeranyltransferase I is essential for dendritic development of cerebellar Purkinje cells
title_short Geranylgeranyltransferase I is essential for dendritic development of cerebellar Purkinje cells
title_sort geranylgeranyltransferase i is essential for dendritic development of cerebellar purkinje cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902468/
https://www.ncbi.nlm.nih.gov/pubmed/20540740
http://dx.doi.org/10.1186/1756-6606-3-18
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