Ca2+ influx through P2X receptors induces actin cytoskeleton reorganization by the formation of cofilin rods in neurites
Ca2+ influx through P2X receptors induces actin cytoskeleton reorganization by the formation of cofilin rods in neurites
复制标题
DOI：
10.1016/j.mcn.2007.10.001
复制
发表时间：
2008-02-01
影响因子：
3.5
通讯作者：
Oka, Kotaro
中科院分区：
文献类型：
--
作者：
Homma, Kohei;Niino, Yusuke;Oka, Kotaro
在生理和病理事件中，细胞外ATP通过控制几种类型的嘌呤能受体和改变细胞骨架动力学起着重要作用。为了了解ATP依赖的细胞骨架重塑过程，我们以肌动蛋白细胞骨架的关键调节因子cofilin为研究对象，通过荧光蛋白标记的cofilin和actin、Ca 2+成像和荧光共振能量转移（FRET）技术研究了cofilin在PC 12细胞中的动态变化。结果，ATP诱导细胞内Ca ~（2+）增加，伴随着cofilin杆的形成。在表达cofilin的非磷酸化变体的细胞中没有观察到ATP诱导的cofilin杆的形成。P2 X受体激动剂诱导了cofilin棒状体的形成，而钙调蛋白和钙调神经磷酸酶抑制剂则抑制了cofilin棒状体的形成，表明钙离子通过P2 X受体内流，通过钙调神经磷酸酶依赖的cofilin去磷酸化作用诱导了cofilin棒状体的形成。该通路可能是解释ATP对神经元发育和损伤的影响的候选者之一。(C)2007年爱思唯尔公司All rights reserved.
In physiological and pathological events, extracellular ATP plays an important role by controlling several types of purinergic receptors and changing cytoskeleton dynamics. To know the process of ATP-dependent cytoskeleton remodeling, we focused on cofilin, a key regulator of actin cytoskeleton, and investigated the dynamics of cofilin in PC12 cells through fluorescent protein-labeled cofilin and actin, Ca2+ imaging, and fluorescence resonance energy transfer (FRET) techniques. As a result, ATP induced intracellular Ca2+ increase, following cofilin rods' formation. ATP-induced cofilin rods' formation was not observed in cells expressing unphosphorylatable variant of cofilin. A P2X receptor agonist, but not P2Y, induced the formation of cofilin rods, whereas calmodulin and calcineurin inhibitors suppressed it. These results indicate that Ca2+ influx through P2X receptors induces the formation of cofilin rods via calcineurin-dependent dephosphorylation of cofilin. This pathway might be one candidate to explain the effects of ATP on neuronal development and injury. (C) 2007 Elsevier Inc. All rights reserved.