How does calcium interact with the cytoskeleton to regulate growth cone motility during axon pathfinding?
How does calcium interact with the cytoskeleton to regulate growth cone motility during axon pathfinding?
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DOI：
10.1016/j.mcn.2017.07.006
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发表时间：
2017-10-01
影响因子：
3.5
通讯作者：
Foa, Lisa
中科院分区：
文献类型：
--
作者：
Gasperini, Robert J.;Pavez, Macarena;Foa, Lisa
神经元形成连接的精确性对于神经系统的正常发育和功能至关重要。神经系统中神经元回路的发育是通过轴突寻路来完成的：生长锥引导轴突通过胚胎环境与其适当的突触伴侣连接以形成功能回路的过程。尽管多年来一直在努力了解这一过程是如何调节的，但控制生长锥细胞骨架和运动性的完整分子机制仍然没有得到解决。轴突导向领域的中心原则是钙信号通过调节生长锥细胞骨架的重排来调节生长锥行为，例如延伸、转动和暂停。在这里，我们提供的证据表明，不仅钙信号的幅度是至关重要的生长锥运动，而且钙动员的来源。我们提供了一个例子，这一想法，通过证明，操纵钙信号通过L型电压门控钙通道可以扰乱感觉神经元运动的netrin-1的来源。理解钙信号如何被转导以启动细胞骨架变化代表了我们目前对支配轴突引导的机制的知识中的一个重大空白，从而在发育中的神经系统中形成功能性神经回路。
The precision with which neurons form connections is crucial for the normal development and function of the nervous system. The development of neuronal circuitry in the nervous system is accomplished by axon path- finding: a process where growth cones guide axons through the embryonic environment to connect with their appropriate synaptic partners to form functional circuits. Despite intense efforts over many years to understand how this process is regulated, the complete repertoire of molecular mechanisms that govern the growth cone cytoskeleton and hence motility, remain unresolved. A central tenet in the axon guidance field is that calcium signals regulate growth cone behaviours such as extension, turning and pausing by regulating rearrangements of the growth cone cytoskeleton. Here, we provide evidence that not only the amplitude of a calcium signal is critical for growth cone motility but also the source of calcium mobilisation. We provide an example of this idea by demonstrating that manipulation of calcium signalling via L-type voltage gated calcium channels can perturb sensory neuron motility towards a source of netrin-1. Understanding how calcium signals can be transduced to initiate cytoskeletal changes represents a significant gap in our current knowledge of the mechanisms that govern axon guidance, and consequently the formation of functional neural circuits in the developing nervous system.