The Drosophila receptor guanylyl cyclase Gyc76C is required for semaphorin-1a-plexin A-mediated axonal repulsion
The Drosophila receptor guanylyl cyclase Gyc76C is required for semaphorin-1a-plexin A-mediated axonal repulsion
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DOI：
10.1523/jneurosci.1104-04.2004
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发表时间：
2004-07-28
影响因子：
5.3
通讯作者：
Kolodkin, AL
中科院分区：
文献类型：
--
作者：
Ayoob, JC;Yu, HH;Kolodkin, AL
延伸生长锥内的环核苷酸水平影响导航轴突对引导线索的反应。体外 cAMP 或 cGMP 信号传导的药理学改变显着调节生长锥对引诱剂和驱避剂的反应，尽管这些第二信使在体内引导信号传导级联背景下如何发挥作用尚不清楚。我们在此报告，果蝇受体型鸟苷酸环化酶 Gyc76C 是 semaphorin-1a (Sema-1a)-plexin A 排斥轴突体内运动轴突引导所必需的。我们的遗传分析定义了轴突排斥中神经元对 Gyc76C 的需求。此外，我们发现 Gyc76C 催化环化酶结构域的完整性对于 Sema-1a 轴突排斥中的 Gyc76C 功能至关重要。我们的结果支持一个模型，其中 Gyc76C 产生的 cGMP 促进 Sema-1a-plexin A 介导的运动轴突解聚，从而在发育中的果蝇胚胎中产生神经肌肉连接。
Cyclic nucleotide levels within extending growth cones influence how navigating axons respond to guidance cues. Pharmacological alteration of cAMP or cGMP signaling in vitro dramatically modulates how growth cones respond to attractants and repellents, although how these second messengers function in the context of guidance cue signaling cascades in vivo is poorly understood. We report here that the Drosophila receptor-type guanylyl cyclase Gyc76C is required for semaphorin-1a (Sema-1a)-plexin A repulsive axon guidance of motor axons in vivo. Our genetic analyses define a neuronal requirement for Gyc76C in axonal repulsion. Additionally, we find that the integrity of the Gyc76C catalytic cyclase domain is critical for Gyc76C function in Sema-1a axon repulsion. Our results support a model in which cGMP production by Gyc76C facilitates Sema-1a-plexin A-mediated defasciculation of motor axons, allowing for the generation of neuromuscular connectivity in the developing Drosophila embryo.