The Center for Autoimmune and Musculoskeletal Disease, The Feinstein Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030, USA.
Mol Cell Neurosci. 2011 Dec;48(4):339-48. doi: 10.1016/j.mcn.2011.04.003. Epub 2011 Apr 23.
Two central challenges for the field of neurobiology are to understand how axons grow and make proper synaptic connections under normal conditions and how they repair their membranes and mount regenerative responses after injury. At the most reductionist level, the first step toward addressing these challenges is to delineate the cellular and molecular processes by which an axon extends from its cell body. Underlying axon extension are questions of appropriate timing and mechanisms that establish or maintain the axon's polarity, initiate growth cone formation, and promote axon outgrowth and synapse formation. After injury, the problem is even more complicated because the neuron must also repair its damaged membrane, redistribute or manufacture what it needs in order to survive, and grow and form new synapses within a more mature, complex environment. While other reviews have focused extensively on the signaling events and cytoskeletal rearrangements that support axon outgrowth and regeneration, we focus this review instead on the underlying membrane trafficking events underlying these processes. Though the mechanisms are still under active investigation, the key roles played by membrane trafficking events during axon repair, growth, and regeneration have been elucidated through elegant comparative studies in both invertebrate and vertebrate organisms. Taken together, a model emerges indicating that the critical requirements for ensuring proper membrane sealing and axon extension include iterative bouts of SNARE mediated exocytosis, endocytosis, and functional links between vesicles and the actin cytoskeleton, similar to the mechanisms utilized during synaptic transmission. This article is part of a Special Issue entitled 'Neuronal Function'.
神经生物学领域面临的两个主要挑战是，了解轴突在正常条件下如何生长并形成适当的突触连接，以及它们在受伤后如何修复其膜并进行再生反应。在最简化的层面上，解决这些挑战的第一步是阐明轴突从细胞体延伸的细胞和分子过程。轴突延伸的基础是关于适当的时间安排和机制的问题，这些问题决定或维持轴突的极性、启动生长锥形成以及促进轴突生长和突触形成。受伤后，问题更加复杂，因为神经元还必须修复受损的膜，重新分配或制造其生存所需的物质，并在更成熟、复杂的环境中生长和形成新的突触。虽然其他综述广泛关注支持轴突生长和再生的信号事件和细胞骨架重排，但我们重点关注这些过程背后的基本膜运输事件。虽然这些机制仍在积极研究中，但通过在无脊椎动物和脊椎动物生物体中进行的巧妙比较研究，已经阐明了膜运输事件在轴突修复、生长和再生中的关键作用。总的来说，出现了一个模型，表明确保适当的膜密封和轴突延伸的关键要求包括 SNARE 介导的胞吐作用、内吞作用和囊泡与肌动蛋白细胞骨架之间的功能连接的反复爆发，类似于在突触传递中使用的机制。本文是题为“神经元功能”的特刊的一部分。
