The target of rapamycin complex 2 controls dendritic tiling of Drosophila sensory neurons through the Tricornered kinase signalling pathway

The target of rapamycin complex 2 controls dendritic tiling of Drosophila sensory neurons through the Tricornered kinase signalling pathway
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DOI:
10.1038/emboj.2009.312
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发表时间:
2009-12-16
期刊:
影响因子:
11.4
通讯作者:
Emoto, Kazuo
Emoto, Kazuo
中科院分区:
生物学1区
文献类型:
--
作者:
Koike-Kumagai, Makiko;Yasunaga, Kei-ichiro;Emoto, Kazuo

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为了完全和非冗余地覆盖感受野,某些功能群的神经元排列其树突的瓦片。在果蝇IV类树突树枝化(da)神经元中,NDR家族激酶Tricorned(Trc)是促进树突平铺的树突同型排斥所必需的。我们在这里报告,Sin 1,Rictor,和雷帕霉素(TOR)的目标,TOR复合物2(TORC 2)的组成部分,所需的树突状平铺IV类DA神经元。类似于trc突变体,sin 1和rictor突变体的树突显示出不适当的树突区域重叠。TORC 2组分在物理和遗传上与Trc相互作用,这与调节树突平铺的共同作用一致。此外,T0 RC 2对于Trc在体内和体外活性的关键残基上的Trc磷酸化是必需的。值得注意的是,神经元表达的显性活性形式的Trc拯救sin 1和rictor突变体的平铺缺陷。这些发现表明,TORC 2可能与Trc信号通路一起调节IV da类神经元的树突状平铺,从而揭示TORC 2在体内的第一个神经元功能。The EMBO Journal(2009)28,3879-3892. doi:10.1038/doj.2009.312; 2009年10月29日在线发布
To cover the receptive field completely and non-redundantly, neurons of certain functional groups arrange tiling of their dendrites. In Drosophila class IV dendrite arborization (da) neurons, the NDR family kinase Tricornered (Trc) is required for homotypic repulsion of dendrites that facilitates dendritic tiling. We here report that Sin1, Rictor, and target of rapamycin (TOR), components of the TOR complex 2 (TORC2), are required for dendritic tiling of class IV da neurons. Similar to trc mutants, dendrites of sin1 and rictor mutants show inappropriate overlap of the dendritic fields. TORC2 components physically and genetically interact with Trc, consistent with a shared role in regulating dendritic tiling. Moreover, TORC2 is essential for Trc phosphorylation on a residue that is critical for Trc activity in vivo and in vitro. Remarkably, neuronal expression of a dominant active form of Trc rescues the tiling defects in sin1 and rictor mutants. These findings suggest that TORC2 likely acts together with the Trc signalling pathway to regulate the dendritic tiling of class IV da neurons, and thus uncover the first neuronal function of TORC2 in vivo. The EMBO Journal (2009) 28, 3879-3892. doi: 10.1038/emboj.2009.312; Published online 29 October 2009