RPM-1 is localized to distinct subcellular compartments and regulates axon length in GABAergic motor neurons.
RPM-1 is localized to distinct subcellular compartments and regulates axon length in GABAergic motor neurons.
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DOI：
10.1186/1749-8104-9-10
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发表时间：
2014-05-10
影响因子：
3.6
通讯作者：
Grill B
中科院分区：
文献类型：
--
作者：
Opperman KJ;Grill B
PAM/Highwire/RPM-1（PHR）蛋白是在发育过程中调节轴突长度和突触形成的保守信号蛋白。秀丽隐杆线虫rpm-1的功能丧失导致机械感觉神经元的轴突终止和突触形成缺陷。为什么这两种表型在单个神经元细胞中观察到的解释仍然缺乏。此外，还不确定在rpm-1突变体的机械感觉神经元中观察到的轴突终止表型是否是这种特定类型的神经元所特有的，或者是rpm-1功能丧失时发生的更广泛的缺陷。在这里，我们表明，RPM-1是本地化的成熟轴突尖端和突触前终端的个别运动神经元和个别mechanosensory神经元。遗传分析表明，GABA能运动神经元，像机械感觉神经元，在rpm-1突变体中具有突触形成和轴突终止缺陷。RPM-1与活动区成分SYD-2（Liprin）平行发挥作用，不仅调节突触形成，还调节运动神经元中的轴突终止。我们对rpm-1−/−; syd-2−/−双突变体的分析也揭示了RPM-1在轴突延伸中的作用。MAP 3 K DLK-1部分介导RPM-1在轴突终止和轴突延伸中的功能，DLK-1的相对作用由所讨论的神经元的解剖位置决定。我们的研究结果表明，轴突终止缺陷是一个核心表型引起的功能丧失的rpm-1，而不是唯一的机械感觉神经元。我们在运动神经元和机械感觉神经元中发现RPM-1定位于单个细胞中的多个不同的亚细胞区室。因此，RPM-1可能受到差异调节，或者RPM-1可能在不同的亚细胞区室中差异控制信号，以调节单个神经元中的多种发育结果。我们的研究结果为先前提出的模型提供了进一步的支持，即PHR蛋白的功能是协调轴突的生长和终止与突触的形成。
The PAM/Highwire/RPM-1 (PHR) proteins are conserved signaling proteins that regulate axon length and synapse formation during development. Loss of function in Caenorhabditis elegans rpm-1 results in axon termination and synapse formation defects in the mechanosensory neurons. An explanation for why these two phenotypes are observed in a single neuronal cell has remained absent. Further, it is uncertain whether the axon termination phenotypes observed in the mechanosensory neurons of rpm-1 mutants are unique to this specific type of neuron, or more widespread defects that occur with loss of function in rpm-1. Here, we show that RPM-1 is localized to both the mature axon tip and the presynaptic terminals of individual motor neurons and individual mechanosensory neurons. Genetic analysis indicated that GABAergic motor neurons, like the mechanosensory neurons, have both synapse formation and axon termination defects in rpm-1 mutants. RPM-1 functions in parallel with the active zone component SYD-2 (Liprin) to regulate not only synapse formation, but also axon termination in motor neurons. Our analysis of rpm-1−/−; syd-2−/− double mutants also revealed a role for RPM-1 in axon extension. The MAP3K DLK-1 partly mediated RPM-1 function in both axon termination and axon extension, and the relative role of DLK-1 was dictated by the anatomical location of the neuron in question. Our findings show that axon termination defects are a core phenotype caused by loss of function in rpm-1, and not unique to the mechanosensory neurons. We show in motor neurons and in mechanosensory neurons that RPM-1 is localized to multiple, distinct subcellular compartments in a single cell. Thus, RPM-1 might be differentially regulated or RPM-1 might differentially control signals in distinct subcellular compartments to regulate multiple developmental outcomes in a single neuron. Our findings provide further support for the previously proposed model that PHR proteins function to coordinate axon outgrowth and termination with synapse formation.