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

Lateral diffusion of inositol 1,4,5-trisphosphate receptor type 1 in Purkinje cells is regulated by calcium and actin filaments
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DOI:
10.1111/j.1471-4159.2010.06885.x
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发表时间:
2010-09-01
影响因子:
4.7
通讯作者:
Mikoshiba, Katsuhiko
Mikoshiba, Katsuhiko
中科院分区:
医学2区
文献类型:
--
作者:
Fukatsu, Kazumi;Bannai, Hiroko;Mikoshiba, Katsuhiko

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1型肌醇1,4,5-三磷酸受体(IP(3)R1)是一种细胞内钙离子释放通道,在浦肯野细胞功能中起重要作用。IP(3)R1在内质网膜上的动态变化和IP(3)R1在神经元中的分布被认为对Ca ~(2+)释放的空间调节是重要的。在这项研究中,我们分析了IP(3)R1在小脑切片培养的浦肯野细胞中的侧向扩散,使用光漂白后的荧光恢复。在浦肯野细胞的树突中,IP(3)R1表现出侧向扩散,有效扩散常数约为0.30 μ m2/s,并且IP(3)R1的扩散受肌动蛋白丝的负调节。我们发现肌动蛋白丝也参与了浦肯野细胞棘中IP(3)R1扩散的调节。谷氨酸或使君子酸刺激,激活谷氨酸受体,并导致浦肯野细胞中的Ca 2+瞬变,减少IP(3)R1的扩散,并增加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IP(3)R1在脊髓中的稳定。
Inositol 1,4,5-trisphosphate receptor type 1 (IP(3)R1) is an intracellular Ca2+ 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 Ca2+ 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 mu m2/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 Ca2+ 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.