Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA.
Dev Neurobiol. 2011 Sep;71(9):795-800. doi: 10.1002/dneu.20908. Epub 2011 Jul 29.
At the distal most aspect of motile extending axons and dendrites lies the growth cone, a hand like macroorganelle of membrane bound cytoskeleton, packed with receptors, adhesion molecules, molecular motors, and an army of regulatory and signaling proteins. Splayed out along the substratum in vitro, the growth cone resembles an open hand with bundles of filamentous actin, barbed ends outstretched, as if fingers extending from a central domain of dynamic microtubule plus ends. The growth cone acts first as a sensory platform, analyzing the environment ahead for the presence of guidance cues, secondly as a mechanical dynamo establishing focal contact with the extracellular matrix to drive processive forward outgrowth, and thirdly as a forward biochemical command center where signals are interrogated to inform turning, extension, retraction, or branching. During his career, Paul Letourneau has made major contributions to our understanding of how growth cones respond to their environment. Here, we will summarize some of these major advances in their historical context. Letourneau's contributions have provided insights into cytoskeletal organization, growth cone dynamics, and signaling pathways. His recent work has described some important molecules and molecular mechanisms involved in growth cone turning. Although much remains to be understood about this important and intriguing structure, Letourneau's contributions have provided us with "growth cone guidance."
在运动延伸的轴突和树突的最远端，是生长锥，这是一种具有膜结合细胞骨架的手状宏观细胞器，充满了受体、黏附分子、分子马达以及一大批调节和信号蛋白。在体外的基质上展开，生长锥类似于张开的手，有束丝状肌动蛋白，伸出有刺的末端，就像从动态微管正极端的中央域延伸出的手指。生长锥首先充当感觉平台，分析前方环境中是否存在导向线索，其次充当机械动力源，与细胞外基质建立焦点接触，以驱动连续向前生长，最后充当向前的生化指挥中心，在那里可以对信号进行询问，以通知转向、延伸、缩回或分支。在他的职业生涯中，Paul Letourneau 为我们理解生长锥如何对其环境做出反应做出了重大贡献。在这里，我们将在历史背景下总结其中的一些主要进展。Letourneau 的贡献提供了对细胞骨架组织、生长锥动力学和信号通路的深入了解。他最近的工作描述了一些与生长锥转向相关的重要分子和分子机制。尽管关于这个重要而有趣的结构还有很多需要了解，但 Letourneau 的贡献为我们提供了“生长锥导向”。
