Abi plays an opposing role to Abl in Drosophila axonogenesis and synaptogenesis
Abi plays an opposing role to Abl in Drosophila axonogenesis and synaptogenesis
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DOI：
10.1242/dev.033324
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发表时间：
2009-09-15
期刊：
影响因子：
4.6
通讯作者：
Juang, Jyh-Lyh
中科院分区：
文献类型：
--
作者：
Lin, Tzu-Yang;Huang, Chiu-Hui;Juang, Jyh-Lyh
Abl 酪氨酸激酶 (Abl) 通过调节肌动蛋白动力学来调节轴突引导。 Abelson 相互作用蛋白 (Abi) 最初被鉴定为 Abl 的激酶底物，也在肌动蛋白动力学中发挥着关键作用，但其相对于 Abl 在神经系统发育中的作用仍不清楚。在这里，我们发现 abi 突变会破坏发育中的果蝇中枢神经系统 (CNS) 的轴突模式。然而，将 abi 基因剂量减少一半可显着挽救 Abl 突变体表型的蛹致死率、轴突引导缺陷和运动缺陷。此外，我们发现 Abl 突变会增加神经肌肉接头处的突触生长和自发突触传递频率。 abi 和启用 (ena) 的双杂合性也抑制 Abl 突变体的突触过度生长表型，表明 Abi 与 Ena 协同作用，拮抗突触发生中的 Abl 功能。有趣的是，在培养细胞中单独过度表达 Abi 或 Ena 会显着地将外周 F-肌动蛋白重新分配到细胞质，并与 Abi 和/或 Ena 共定位聚集体，并导致神经突延伸减少。然而，共表达 Abl 与 Abi 或 Ena 将细胞质 F-肌动蛋白重新分布回细胞外周并恢复双极细胞形态。这些数据表明abi和Abl在果蝇轴突发生和突触发生中具有拮抗相互作用，这可能是通过调节F-肌动蛋白重组而发生的。
Abl tyrosine kinase (Abl) regulates axon guidance by modulating actin dynamics. Abelson interacting protein (Abi), originally identified as a kinase substrate of Abl, also plays a key role in actin dynamics, yet its role with respect to Abl in the developing nervous system remains unclear. Here we show that mutations in abi disrupt axonal patterning in the developing Drosophila central nervous system (CNS). However, reducing abi gene dosage by half substantially rescues Abl mutant phenotypes in pupal lethality, axonal guidance defects and locomotion deficits. Moreover, we show that mutations in Abl increase synaptic growth and spontaneous synaptic transmission frequency at the neuromuscular junction. Double heterozygosity for abi and enabled (ena) also suppresses the synaptic overgrowth phenotypes of Abl mutants, suggesting that Abi acts cooperatively with Ena to antagonize Abl function in synaptogenesis. Intriguingly, overexpressing Abi or Ena alone in cultured cells dramatically redistributed peripheral F-actin to the cytoplasm, with aggregates colocalizing with Abi and/or Ena, and resulted in a reduction in neurite extension. However, co-expressing Abl with Abi or Ena redistributed cytoplasmic F-actin back to the cell periphery and restored bipolar cell morphology. These data suggest that abi and Abl have an antagonistic interaction in Drosophila axonogenesis and synaptogenesis, which possibly occurs through the modulation of F-actin reorganization.