Laboratory for Neuronal Growth Mechanisms, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
Neurosci Res. 2012 Aug;73(4):269-74. doi: 10.1016/j.neures.2012.05.010. Epub 2012 Jun 7.
The formation of precise neuronal networks is critically dependent on the motility of axonal growth cones. Extracellular gradients of guidance cues evoke localized Ca(2+) elevations to attract or repel the growth cone. Recent studies strongly suggest that the polarity of growth cone guidance, with respect to the localization of Ca(2+) signals, is determined by Ca(2+) release from the endoplasmic reticulum (ER) in the following manner: Ca(2+) signals containing ER Ca(2+) release cause growth cone attraction, while Ca(2+) signals without ER Ca(2+) release cause growth cone repulsion. Recent studies have also shown that exocytic and endocytic membrane trafficking can drive growth cone attraction and repulsion, respectively, downstream of Ca(2+) signals. Most likely, these two mechanisms underlie cue-induced axon guidance, in which a localized imbalance between exocytosis and endocytosis dictates bidirectional growth cone steering. In this Update Article, I summarize recent advances in growth cone research and propose that polarized membrane trafficking plays an instructive role to spatially localize steering machineries, such as cytoskeletal components and adhesion molecules.
精确的神经元网络的形成严重依赖于轴突生长锥的运动性。细胞外导向线索的梯度引发局部 Ca(2+) 升高，吸引或排斥生长锥。最近的研究强烈表明，相对于 Ca(2+) 信号的定位，生长锥导向的极性是通过内质网 (ER) 中的 Ca(2+) 释放以以下方式确定的：包含 ER Ca(2+) 释放的 Ca(2+) 信号引起生长锥吸引，而不包含 ER Ca(2+) 释放的 Ca(2+) 信号引起生长锥排斥。最近的研究还表明，胞吐作用和胞吞作用的膜转运可以分别在 Ca(2+) 信号的下游驱动生长锥的吸引和排斥。很可能，这两种机制构成了线索诱导的轴突导向的基础，其中胞吐作用和胞吞作用之间的局部不平衡决定了双向生长锥转向。在这篇综述文章中，我总结了生长锥研究的最新进展，并提出极化的膜转运在空间定位转向机制（如细胞骨架成分和粘附分子）方面发挥指导作用。
