UNC-6/netrin and SLT-1/slit guidance cues orient axon outgrowth mediated by MIG-10/RIAM/lamellipodin
UNC-6/netrin and SLT-1/slit guidance cues orient axon outgrowth mediated by MIG-10/RIAM/lamellipodin
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DOI：
10.1016/j.cub.2006.03.025
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发表时间：
2006-05-09
期刊：
影响因子：
9.2
通讯作者：
Wadsworth, William G.
中科院分区：
文献类型：
--
作者：
Quinn, Christopher C.;Pfeil, Douglas S.;Wadsworth, William G.
背景：轴突迁移是由细胞外信号引导的，这些信号可以作为排斥剂或引诱剂。然而，吸引和排斥反应的决定方式背后的逻辑尚不清楚。许多细胞外的引导信号，和细胞成分，介导他们的信号，已经牵连在这两种类型的responses.Results：遗传分析表明，β-10/RIAM/lamelliodin，胞质衔接蛋白，功能下游的吸引性引导信号β-6/ netrin和排斥性引导信号β-1/slit，以指导腹侧迁移的AVM和PVM轴突在C。优雅的。此外，在不存在IFN-6和IFN-1的情况下，IFN-10的过表达诱导了具有非定向生长的多极表型。添加β-6或β-1会导致神经元变成单极。此外，通过过表达β-10，β-6或β-1向腹侧引导轴突的能力增强。我们还表明，之间的相互作用，促进肌动蛋白丝的延伸，是重要的，在响应的指导线索，并与肌动蛋白在培养的细胞，在那里它可以诱导形成lamellipodi.Conclusions：我们的结论是，<$-10介导的指导AVM和PVM轴突响应细胞外<$-6和<$-1的指导线索。吸引性和排斥性的引导线索定向依赖于β-10的轴突生长，以引起定向反应。
Background: Axon migrations are guided by extracellular cues that can act as repellants or attractants. However, the logic underlying the manner through which attractive and repulsive responses are determined is unclear. Many extracellular guidance cues, and the cellular components that mediate their signals, have been implicated in both types of responses.Results: Genetic analyses indicate that MIG-10/RIAM/ lamellipodin, a cytoplasmic adaptor protein, functions downstream of the attractive guidance cue UNC-6/ netrin and the repulsive guidance cue SLT-1/slit to direct the ventral migration of the AVM and PVM axons in C. elegans. Furthermore, overexpression of MIG-10 in the absence of UNC-6 and SLT-1 induces a multipolar phenotype with undirected outgrowths. Addition of either UNC-6 or SLT-1 causes the neurons to become monopolar. Moreover, the ability of UNC-6 or SLT-1 to direct the axon ventrally is enhanced by the MIG-10 overexpression. We also demonstrate that an interaction between MIG-10 and UNC-34, a protein that promotes actin-filament extension, is important in the response to guidance cues and that MIG-10 colocalizes with actin in cultured cells, where it can induce the formation of lamellipodia.Conclusions: We conclude that MIG-10 mediates the guidance of AVM and PVM axons in response to the extracellular UNC-6 and SLT-1 guidance cues. The attractive and repulsive guidance cues orient MIG-10-dependant axon outgrowth to cause a directional response.