Local caspase activation interacts with Slit-Robo signaling to restrict axonal arborization.
Local caspase activation interacts with Slit-Robo signaling to restrict axonal arborization.
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DOI：
10.1083/jcb.201303072
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发表时间：
2013-11-25
期刊：
影响因子：
--
通讯作者：
Okamoto H
中科院分区：
文献类型：
--
作者：
Campbell DS;Okamoto H
在中枢神经系统中，轴突分支点的局部半胱天冬酶激活通过与Slit 1a-Robo 2信号相互作用来限制乔木生长和突触发生。除了对细胞凋亡至关重要之外，细胞凋亡途径的组分，如半胱天冬酶，还参与许多类型细胞（包括神经元）的其他生理过程。然而，很少有人知道他们在动态的，非物理破坏性的过程中，如轴突分支和突触发生的作用。我们发现，半胱天冬酶在年轻的，动态的视网膜神经节细胞轴突乔木的分支点，但不是在细胞体或稳定的成熟乔木在体内局部活跃。依赖于Caspase-3、Caspase-9和p38丝裂原活化蛋白激酶（MAPK）的Caspase活化在对应于分支尖端添加的分支点迅速增加。延时成像显示，Caspase-3和Caspase-9的敲低导致更稳定的乔木和突触前位点。遗传分析表明，Caspase-3，Caspase-9，和p38 MAPK与Slit 1a-Robo 2信号相互作用，表明caspase的局部激活位于配体受体系统的下游，作为轴突分支尖端和突触动力学的关键启动子，以限制中枢神经系统中的乔木生长。
Local caspase activation at axonal branch points restricts arbor growth and synaptogenesis by interacting with Slit1a-Robo2 signaling in the central nervous system. In addition to being critical for apoptosis, components of the apoptotic pathway, such as caspases, are involved in other physiological processes in many types of cells, including neurons. However, very little is known about their role in dynamic, nonphysically destructive processes, such as axonal arborization and synaptogenesis. We show that caspases were locally active in vivo at the branch points of young, dynamic retinal ganglion cell axonal arbors but not in the cell body or in stable mature arbors. Caspase activation, dependent on Caspase-3, Caspase-9, and p38 mitogen-activated protein kinase (MAPK), rapidly increased at branch points corresponding with branch tip addition. Time-lapse imaging revealed that knockdown of Caspase-3 and Caspase-9 led to more stable arbors and presynaptic sites. Genetic analysis showed that Caspase-3, Caspase-9, and p38 MAPK interacted with Slit1a-Robo2 signaling, suggesting that localized activation of caspases lie downstream of a ligand receptor system, acting as key promoters of axonal branch tip and synaptic dynamics to restrict arbor growth in vivo in the central nervous system.
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