Constitutively active myosin light chain kinase alters axon guidance decisions in Drosophila embryos
Constitutively active myosin light chain kinase alters axon guidance decisions in Drosophila embryos
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DOI：
10.1006/dbio.2002.0768
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发表时间：
2002-09-15
影响因子：
2.7
通讯作者：
VanBerkum, MFA
中科院分区：
文献类型：
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作者：
Kim, YS;Fritz, JL;VanBerkum, MFA
常规的肌球蛋白II活性为轴突生长提供动力，但是为了在轴突通路形成期间实现定向运动，肌球蛋白活性应该通过引导轴突到达其目标的吸引和排斥引导线索来调节。在这里，这种调节的证据是通过使用组成型活性肌球蛋白轻链激酶（ctMLCK）选择性地提高肌球蛋白II活性在果蝇中枢神经系统神经元。ctMLCK在全神经元或主要在pCC/MP2神经元中的表达导致这些轴突不正确地穿过中线。这在不改变细胞命运的情况下发生，并且对调节轻链中的突变敏感。这些结果证实了在轴突通路形成过程中调节肌球蛋白II活性的重要性。中线排斥配体Slit或其受体Roundabout的突变增强了ctMLCK诱导的交叉的数量，但ctMLCK表达也部分挽救了无连合突变体中的连合形成，其中排斥信号仍然很高。Frazzled（中线吸引Netrins的受体）的过表达增强ctMLCK依赖性交叉，但当Frazzled活性通过使用功能丧失突变而降低时，交叉被抑制。这些结果证实，适当的途径形成需要仔细调节MLCK和/或肌球蛋白II的活性，并建议调节发生在直接响应吸引和排斥线索。(C)2002 Elsevier Science（美国）。
Conventional myosin II activity provides the motile force for axon outgrowth, but to achieve directional movement during axon pathway formation, myosin activity should be regulated by the attractive and repulsive guidance cues that guide an axon to its target. Here, evidence for this regulation is obtained by using a constitutively active Myosin Light Chain Kinase (ctMLCK) to selectively elevate myosin II activity in Drosophila CNS neurons. Expression of ctMLCK pan-neurally or in primarily pCC/MP2 neurons causes these axons to cross the midline incorrectly. This occurs without altering cell fates and is sensitive to mutations in the regulatory light chains. These results confirm the importance of regulating myosin II activity during axon pathway formation. Mutations in the midline repulsive ligand Slit, or its receptor Roundabout, enhance the number of ctMLCK-induced crossovers, but ctMLCK expression also partially rescues commissure formation in commissureless mutants, where repulsive signals remain high. Overexpression of Frazzled, the receptor for midline attractive Netrins, enhances ctMLCK-dependent crossovers, but crossovers are suppressed when Frazzled activity is reduced by using loss-of-function mutations. These results confirm that proper pathway formation requires careful regulation of MLCK and/or myosin II activity and suggest that regulation occurs in direct response to attractive and repulsive cues. (C) 2002 Elsevier Science (USA).