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首页> 外文期刊>The European Journal of Neuroscience >Acetylcholine receptors are required for postsynaptic aggregation driven by the agrin signalling pathway.
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Acetylcholine receptors are required for postsynaptic aggregation driven by the agrin signalling pathway.

机译:凝集素信号传导途径驱动的突触后聚集需要乙酰胆碱受体。

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摘要

To investigate the role of acetylcholine receptors (AChRs) in the aggregation of postsynaptic molecules on muscle cells, we utilized the 1R- genetic variant of C2 muscle cells which has very little expression of AChRs in its cell membrane. On C2 myotubes, AChRs cluster spontaneously, with the frequency of clustering greatly enhanced by motor neuron-derived agrin. Signal transduction events driven by agrin, including the tyrosine phosphorylation of muscle-specific kinase (MuSK) and the AChR beta subunit, have been implicated as requirements of postsynaptic scaffold assembly. We show here that some molecules of the postsynaptic scaffold spontaneously aggregate and colocalize on 1R- myotubes at very low frequency, including an as yet unidentified agrin binding molecule, beta-dystroglycan and MuSK. Agrin is unable to increase the frequency of these aggregations, but does cause tyrosine phosphorylation of MuSK. We conclude that free molecules can associate into aggregates independently of AChRs, but AChRs are required for high-frequency molecular aggregation driven by the agrin signalling pathway. MuSK tyrosine phosphorylation appears to precede a requisite event involving AChRs that aggregates postsynaptic molecules.
机译:为了研究乙酰胆碱受体(AChRs)在肌肉细胞上突触后分子聚集中的作用,我们利用了C2肌肉细胞的1R基因变异,在其细胞膜中几乎没有AChRs表达。在C2肌管上,AChRs自发聚集,并且聚集的频率通过运动神经元衍生的凝集素大大提高。凝集素驱动的信号转导事件,包括肌肉特异性激酶(MuSK)和AChRβ亚基的酪氨酸磷酸化,被认为是突触后支架组装的要求。我们在这里显示突触后支架的一些分子自发聚集并以非常低的频率共定位于1R-肌管上,包括尚未确定的凝集素结合分子,β-dystroglycan和MuSK。 Agrin不能增加这些聚集的频率,但是会引起MuSK的酪氨酸磷酸化。我们得出的结论是,游离分子可以独立于AChRs缔合成聚集体,但是AChRs是凝集素信号通路驱动的高频分子聚集所必需的。 MuSK酪氨酸磷酸化似乎发生在涉及聚集突触后分子的AChR的必要事件之前。

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