Calyculin A-induced neurite retraction is critically dependent on actomyosin activation but not on polymerization state of microtubules.
Calyculin A-induced neurite retraction is critically dependent on actomyosin activation but not on polymerization state of microtubules.
复制标题
Calyculin A 诱导的神经突回缩主要依赖于肌动球蛋白的激活，但不依赖于微管的聚合状态。
DOI：
10.1016/j.bbrc.2009.10.108
复制
发表时间：
2009
影响因子：
3.1
通讯作者：
Y. Fujiyoshi
中科院分区：
文献类型：
--
作者：
Ayumu Inutsuka;M. Goda;Y. Fujiyoshi
Calyculin A (CL-A) 是一种从海洋海绵 Discodermia 花萼中分离出来的毒素，是蛋白磷酸酶 1 (PP1) 和 2A (PP2A) 的强抑制剂。尽管已知 CL-A 会在发育中的神经元中诱导神经突快速回缩，但这种回缩的细胞骨架动力学仍不清楚。在这里，我们使用荧光显微镜和偏光显微镜研究了 CL-A 诱导培养的大鼠海马神经元神经突收缩过程中的细胞骨架动力学，该显微镜可以可视化活细胞中细胞骨架的聚合状态。我们观察到，神经突收缩期间，MT 发生弯曲，同时保持其聚合状态。此外，我们还发现，当MT被诺考达唑解聚或紫杉醇稳定时，CL-A仍然诱导神经突回缩。这些结果表明 CL-A 诱导的神经突回缩除了 MT 解聚之外还有其他机制。我们的药理学研究表明，blebbistatin 和细胞松弛素 D（肌球蛋白 II 的抑制剂和肌动蛋白的解聚剂）可强烈抑制 CL-A 诱导的神经突回缩。基于所有这些发现，我们提出 CL-A 通过肌动球蛋白产生强大的收缩力，从而独立于 MT 解聚而诱导神经突快速收缩。
Calyculin A (CL-A), a toxin isolated from the marine sponge Discodermia calyx, is a strong inhibitor of protein phosphatase 1 (PP1) and 2A (PP2A). Although CL-A is known to induce rapid neurite retraction in developing neurons, the cytoskeletal dynamics of this retraction have remained unclear. Here, we investigated the cytoskeletal dynamics during CL-A-induced neurite retraction in cultured rat hippocampal neurons, using fluorescence microscopy as well as polarized light microscopy, which can visualizes the polymerization state of the cytoskeleton in living cells. We observed that MTs were bent while maintaining their polymerization state during the neurite retraction. In addition, we also found that CL-A still induced neurite retraction when MTs were depolymerized by nocodazole or stabilized by paclitaxel. These results imply a mechanism other than depolymerization of MTs for CL-A-induced neurite retraction. Our pharmacological studies showed that blebbistatin and cytochalasin D, an inhibitor of myosin II and a depolymerizer of actin, strongly inhibited CL-A-induced neurite retraction. Based on all these findings, we propose that CL-A generates strong contractile forces by actomyosin to induce rapid neurite retraction independently from MT depolymerization.
登录
查看更多内容
影响因子：
3.3
作者：
Katoh, K;Hammar, K;Oldenbourg, R
通讯作者：
Oldenbourg, R
影响因子：
--
作者：
Henson, JH;Kolnik, SE;Trabosh, VA
通讯作者：
Trabosh, VA
DOI：
10.1016/0006-291x(89)92189-x
发表时间：
1989-03-31
影响因子：
3.1
作者：
ISHIHARA, H;MARTIN, BL;HARTSHORNE, DJ
通讯作者：
HARTSHORNE, DJ
轻链残基苏氨酸18和丝氨酸19磷酸化对平滑肌肌球蛋白性质和构象的影响。
DOI：
--
发表时间：
1988
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Ikebe,M;Koretz,J;Hartshorne,DJ
通讯作者：
Hartshorne,DJ