The Arp2/3 complex, UNC-115/abLIM, and UNC-34/Enabled regulate axon guidance and growth cone filopodia formation in Caenorhabditis elegans.
The Arp2/3 complex, UNC-115/abLIM, and UNC-34/Enabled regulate axon guidance and growth cone filopodia formation in Caenorhabditis elegans.
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DOI：
10.1186/1749-8104-4-38
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发表时间：
2009-10-02
影响因子：
3.6
通讯作者：
Lundquist EA
中科院分区：
文献类型：
--
作者：
Norris AD;Dyer JO;Lundquist EA
虽然许多参与轴突导向的分子已被鉴定，但这些分子在轴突生长过程中调节生长锥形态的细胞和分子机制仍有待阐明。生长锥的肌动蛋白细胞骨架是板状伪足和丝状伪足形成的基础，板状伪足和丝状伪足控制着生长锥的生长和导向。Arp 2/3复合物在生长锥丝状伪足形成中的作用一直存在争议，生长锥丝状伪足形成的其他机制仍有待描述。在这里，我们表明，编码Arp 2/3复合物（arx基因）的基因突变引起轴突导向缺陷。对体内生长锥发育的分析表明，arx突变体显示丝状伪足缺陷和生长锥尺寸减小。对活体动物生长锥的延时分析表明，arx突变体影响生长锥丝状伪足形成的速率，但不影响丝状伪足的稳定性或长度。另外两种肌动蛋白调节蛋白，E115/abLIM和E1134/Enabled，以前已经显示出影响轴突导向，与Arp 2/3在轴突导向中的作用重叠，并且也影响丝状伪足起始的速率，但不影响稳定性或长度。我们的研究结果表明，Arp 2/3复合物是所需的细胞自主轴突的指导和生长锥丝状伪足的启动。此外，他们还发现，另外两种肌动蛋白结合蛋白，E115/abLIM和E134/Enabled，也控制着生长锥丝状伪足的形成，可能与Arp 2/3平行。这些研究表明，在体内，多种肌动蛋白调节途径，包括Arp 2/3复合物有助于生长锥丝状伪足的形成过程中生长锥生长。
While many molecules involved in axon guidance have been identified, the cellular and molecular mechanisms by which these molecules regulate growth cone morphology during axon outgrowth remain to be elucidated. The actin cytoskeleton of the growth cone underlies the formation of lamellipodia and filopodia that control growth cone outgrowth and guidance. The role of the Arp2/3 complex in growth cone filopodia formation has been controversial, and other mechanisms of growth cone filopodia formation remain to be described. Here we show that mutations in genes encoding the Arp2/3 complex (arx genes) caused defects in axon guidance. Analysis of developing growth cones in vivo showed that arx mutants displayed defects in filopodia and reduced growth cone size. Time-lapse analysis of growth cones in living animals indicated that arx mutants affected the rate of growth cone filopodia formation but not filopodia stability or length. Two other actin modulatory proteins, UNC-115/abLIM and UNC-34/Enabled, that had been shown previously to affect axon guidance had overlapping roles with Arp2/3 in axon guidance and also affected the rate of filopodia initiation but not stability or length. Our results indicate that the Arp2/3 complex is required cell-autonomously for axon guidance and growth cone filopodia initiation. Furthermore, they show that two other actin-binding proteins, UNC-115/abLIM and UNC-34/Enabled, also control growth cone filopodia formation, possibly in parallel to Arp2/3. These studies indicate that, in vivo, multiple actin modulatory pathways including the Arp2/3 complex contribute to growth cone filopodia formation during growth cone outgrowth.
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