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1型肌醇1,4,5-三磷酸受体在浦肯野细胞中的侧向扩散受钙和肌动蛋白丝调节。

Lateral diffusion of inositol 1,4,5-trisphosphate receptor type 1 in Purkinje cells is regulated by calcium and actin filaments.

作者信息

Fukatsu Kazumi, Bannai Hiroko, Inoue Takafumi, Mikoshiba Katsuhiko

机构信息

Laboratory for Developmental Neurobiology, Brain Science Institute RIKEN, Wako, Saitama, Japan.

出版信息

J Neurochem. 2010 Sep;114(6):1720-33. doi: 10.1111/j.1471-4159.2010.06885.x. Epub 2010 Aug 19.

Abstract

Inositol 1,4,5-trisphosphate receptor type 1 (IP(3) R1) is an intracellular Ca(2+) release channel that plays crucial roles in the functions of Purkinje cells. The dynamics of IP(3) R1 on the endoplasmic reticulum membrane and the distribution of IP(3) R1 in neurons are thought to be important for the spatial regulation of Ca(2+) release. In this study, we analyzed the lateral diffusion of IP(3) R1 in Purkinje cells in cerebellar slice cultures using fluorescence recovery after photobleaching. In the dendrites of Purkinje cells, IP(3) R1 showed lateral diffusion with an effective diffusion constant of approximately 0.30 μm(2) /s, and the diffusion of IP(3) R1 was negatively regulated by actin filaments. We found that actin filaments were also involved in the regulation of IP(3) R1 diffusion in the spine of Purkinje cells. Glutamate or quisqualic acid stimulation, which activates glutamate receptors and leads to a Ca(2+) transient in Purkinje cells, decreased the diffusion of IP(3) R1 and increased the density of actin in spines. These findings indicate that the neuronal activity-dependent augmentation of actin contributes to the stabilization of IP(3) R1 in spines.

摘要

1,4,5-三磷酸肌醇受体1型(IP(3)R1)是一种细胞内Ca(2+)释放通道,在浦肯野细胞的功能中起关键作用。内质网膜上IP(3)R1的动力学以及IP(3)R1在神经元中的分布被认为对Ca(2+)释放的空间调节很重要。在本研究中,我们使用光漂白后荧光恢复技术分析了小脑切片培养物中浦肯野细胞内IP(3)R1的横向扩散。在浦肯野细胞的树突中,IP(3)R1表现出横向扩散,有效扩散常数约为0.30μm(2)/s,并且IP(3)R1的扩散受到肌动蛋白丝的负调控。我们发现肌动蛋白丝也参与了浦肯野细胞树突棘中IP(3)R1扩散的调节。谷氨酸或喹啉酸刺激可激活谷氨酸受体并导致浦肯野细胞内Ca(2+)瞬变,减少IP(3)R1的扩散并增加树突棘中肌动蛋白的密度。这些发现表明,神经元活动依赖性的肌动蛋白增加有助于树突棘中IP(3)R1的稳定。

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