Geranylgeranyltransferase I is essential for dendritic development of cerebellar Purkinje cells.
Geranylgeranyltransferase I is essential for dendritic development of cerebellar Purkinje cells.
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香叶基香叶基转移酶 I 对于小脑浦肯野细胞的树突发育至关重要。
DOI：
10.1186/1756-6606-3-18
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发表时间：
2010-06-11
期刊：
影响因子：
3.6
通讯作者：
Luo, Zhen-Ge
中科院分区：
文献类型：
--
作者：
Wu, Kong-Yan;Zhou, Xiu-Ping;Luo, Zhen-Ge
在小脑发育过程中，浦肯野细胞（PC）形成了大脑神经元中最精致的树突树，但PC树枝化的调控机制仍不清楚。香叶基香叶基转移酶I（GGT）是一种异戊烯基转移酶，其负责几种信号蛋白的脂质修饰，例如Rho家族小GTTRac 1，其已被证明参与神经元形态发生。在这里，我们表明，GGT起着重要的作用，在树突状发育的PC。我们发现GGT在发育中的大鼠小脑中大量表达，特别是分子层（ML），富含PC树突的区域。使用小干扰RNA（siRNA）抑制或下调GGT抑制PC的树突发育。相反，GGT的上调促进PC的树突状分支。此外，高K+或脑源性神经营养因子（BDNF）治疗诱导的神经元去极化促进Rac 1和树突发育的PC在培养的小脑切片的膜协会。抑制或下调GGT可抑制BDNF或高K+的作用。我们的研究结果表明，GGT在浦肯野细胞的发育中起着重要的作用，并提出了一个新的作用，GGT在体内神经元形态发生。
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. 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. 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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影响因子：
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