The Role of Apoptotic Signaling in Axon Guidance.
The Role of Apoptotic Signaling in Axon Guidance.
复制标题
DOI：
10.3390/jdb6040024
复制
发表时间：
2018-10-18
影响因子：
2.7
通讯作者：
Kidd T
中科院分区：
文献类型：
--
作者：
Kellermeyer R;Heydman LM;Mastick GS;Kidd T
导航生长锥同时暴露于多个信号，并且必须将竞争性线索整合到连贯的导航响应中。整合的指导线索，传统上认为发生在细胞骨架动力学水平。果蝇的研究表明，细胞表现出低水平的连续半胱天冬酶蛋白酶激活，轴突导向线索可以激活或抑制半胱天冬酶活性。我们根据这些观察建立了一个轴突引导模型。通过类比与其他系统中，半胱天冬酶信号具有非凋亡的功能，我们建议，半胱天冬酶信号可以增强排斥或否定吸引力，以响应外部的指导线索，裂解细胞骨架蛋白。在整个轨迹的过程中，错误导航的轴突可能会超过凋亡的阈值并被淘汰，而做出正确决定的轴突将存活下来。这些观察结果也将解释为什么神经营养因子可以作为轴突导向线索，以及为什么轴突导向系统，如Slit/Robo信号可能作为癌症的肿瘤抑制因子。
Navigating growth cones are exposed to multiple signals simultaneously and have to integrate competing cues into a coherent navigational response. Integration of guidance cues is traditionally thought to occur at the level of cytoskeletal dynamics. Drosophila studies indicate that cells exhibit a low level of continuous caspase protease activation, and that axon guidance cues can activate or suppress caspase activity. We base a model for axon guidance on these observations. By analogy with other systems in which caspase signaling has non-apoptotic functions, we propose that caspase signaling can either reinforce repulsion or negate attraction in response to external guidance cues by cleaving cytoskeletal proteins. Over the course of an entire trajectory, incorrectly navigating axons may pass the threshold for apoptosis and be eliminated, whereas axons making correct decisions will survive. These observations would also explain why neurotrophic factors can act as axon guidance cues and why axon guidance systems such as Slit/Robo signaling may act as tumor suppressors in cancer.