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Interactions between a Receptor Tyrosine Phosphatase and a Cell Surface Ligand Regulate Axon Guidance and Glial-Neuronal Communication

机译:受体酪氨酸磷酸酶和细胞表面配体之间的相互作用调节轴突的指导和神经胶质-神经沟通。

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摘要

We developed a screening method for orphan receptor ligands, in which cell-surface proteins are expressed in Drosophila embryos from GAL4-dependent insertion lines and ligand candidates identified by the presence of ectopic staining with receptor fusion proteins. Stranded at second (Sas) binds to the receptor tyrosine phosphatase Ptp10D in embryos and in vitro. Sas and Ptp10D can interact in trans when expressed in cultured cells. Interactions between Sas and Ptp10D on longitudinal axons are required to prevent them from abnormally crossing the midline. Sas is expressed on both neurons and glia, whereas Ptp10D is restricted to CNS axons. We conducted epistasis experiments by overexpressing Sas in glia and examining how the resulting phenotypes are changed by removal of Ptp10D from neurons. We find that neuronal Ptp10D restrains signaling by overexpressed glial Sas, which would otherwise produce strong glial and axonal phenotypes.
机译:我们开发了一种孤儿受体配体的筛选方法,其中果蝇胚胎中的细胞表面蛋白从依赖GAL4的插入系和通过受体融合蛋白存在异位染色而鉴定的配体候选物中表达。第二链(Sas)在胚胎和体外与受体酪氨酸磷酸酶Ptp10D结合。 Sas和Ptp10D在培养细胞中表达时可以反式相互作用。需要Sas和Ptp10D在纵向轴突之间相互作用,以防止它们异常穿过中线。 Sas在神经元和神经胶质细胞中均表达,而Ptp10D仅限于CNS轴突。我们通过在神经胶质细胞中过度表达Sas进行了上位性实验,并研究了如何通过从神经元中去除Ptp10D来改变所产生的表型。我们发现神经元Ptp10D抑制了过表达的神经胶质Sas的信号传导,否则它会产生强烈的神经胶质和轴突表型。

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