Herzmann Svende, Krumkamp Rafael, Rode Sandra, Kintrup Carina, Rumpf Sebastian
Institute for Neurobiology, University of Münster, Münster, Germany.
Institute for Neurobiology, University of Münster, Münster, Germany
EMBO J. 2017 Jul 3;36(13):1981-1991. doi: 10.15252/embj.201695890. Epub 2017 May 29.
Pruning of unspecific neurites is an important mechanism during neuronal morphogenesis. sensory neurons prune their dendrites during metamorphosis. Pruning dendrites are severed in their proximal regions. Prior to severing, dendritic microtubules undergo local disassembly, and dendrites thin extensively through local endocytosis. Microtubule disassembly requires a katanin homologue, but the signals initiating microtubule breakdown are not known. Here, we show that the kinase PAR-1 is required for pruning and dendritic microtubule breakdown. Our data show that neurons lacking PAR-1 fail to break down dendritic microtubules, and PAR-1 is required for an increase in neuronal microtubule dynamics at the onset of metamorphosis. Mammalian PAR-1 is a known Tau kinase, and genetic interactions suggest that PAR-1 promotes microtubule breakdown largely via inhibition of Tau also in Finally, PAR-1 is also required for dendritic thinning, suggesting that microtubule breakdown might precede ensuing plasma membrane alterations. Our results shed light on the signaling cascades and epistatic relationships involved in neurite destabilization during dendrite pruning.
非特异性神经突的修剪是神经元形态发生过程中的一个重要机制。感觉神经元在变态过程中修剪其树突。正在修剪的树突在其近端区域被切断。在切断之前,树突微管会进行局部解聚,并且树突会通过局部内吞作用大量变细。微管解聚需要一种katanin同源物,但启动微管分解的信号尚不清楚。在这里,我们表明激酶PAR-1是修剪和树突微管分解所必需的。我们的数据表明,缺乏PAR-1的神经元无法分解树突微管,并且PAR-1是变态开始时神经元微管动力学增加所必需的。哺乳动物PAR-1是一种已知的Tau激酶,遗传相互作用表明PAR-1在[此处原文缺失相关内容]中也主要通过抑制Tau来促进微管分解。最后,PAR-1对于树突变细也是必需的,这表明微管分解可能先于随后的质膜改变。我们的结果揭示了树突修剪过程中神经突不稳定所涉及的信号级联和上位关系。