Ca2+ induces macropinocytosis via F-actin depolymerization during growth cone collapse
Ca2+ induces macropinocytosis via F-actin depolymerization during growth cone collapse
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DOI：
10.1016/j.mcn.2008.08.009
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发表时间：
2009-01-05
影响因子：
3.5
通讯作者：
Mikoshiba, Katsuhiko
中科院分区：
文献类型：
--
作者：
Kabayama, Hiroyuki;Nakamura, Takeshi;Mikoshiba, Katsuhiko
生长锥塌陷发生在排斥轴突引导下，并伴随着生长锥质膜表面积的减少。然而，这种减少的机制尚不清楚。在这里，我们证明了在生长锥塌陷期间，咖啡因诱导的钙离子从兰诺定敏感的钙库中释放，通过大吞饮作用触发生长锥中大空泡的形成，胞饮非依赖于细胞质膜的大量回收，以及随后的膜逆行运输。我们观察到咖啡因诱导的大针体面积与生长锥体塌陷有显著的相关性。我们还检测到了信号素3A诱导的巨噬细胞吞噬作用，以及信号素3A诱导的巨噬细胞空泡面积与生长锥体塌陷之间的相关性。此外，F-肌动蛋白解聚的抑制剂jasplakinolide可以阻断咖啡因诱导的巨噬细胞吞噬。我们认为，肌动蛋白细胞骨架重组和巨噬细胞吞噬介导的逆行膜转运的协同调控可能参与了钙离子诱导的轴突生长抑制。(C)2008 Elsevier Inc.保留所有权利。
Growth cone collapse occurs in repulsive axon guidance and is accompanied by a reduction in the surface area of the plasma membrane of growth cones. However, the mechanism of this reduction is unclear. Here, we show that during growth cone collapse, caffeine-induced Ca2+ release from ryanodine-sensitive Ca2+ Stores triggers the formation of large vacuoles in growth cones by macropinocytosis, a clathrin-independent endocytosis for the massive retrieval of the cellular plasma membrane, and Subsequent retrograde membrane transport. We observed a significant correlation of the area of caffeine-induced macropinosomes with growth cone collapse. We also detected macropinocytosis induced by semaphorin 3A, a typical repulsive cue, and correlation between the area of semaphorin 3A-induced macropinocytic vacuoles and growth cone collapse. Moreover, jasplakinolide, an inhibitor of F-actin depolymerization, blocked caffeine-induced macropinocytosis. We propose that the coordinated regulation of actin cytoskeletal reorganization and macropinocytosis-mediated retrograde membrane trafficking may contribute to Ca2+-induced axon growth inhibition. (C) 2008 Elsevier Inc. All rights reserved.