PAR-1 promotes microtubule breakdown during dendrite pruning in Drosophila

被引:34
作者
Herzmann, Svende [1 ]
Krumkamp, Rafael [1 ]
Rode, Sandra [1 ]
Kintrup, Carina [1 ]
Rumpf, Sebastian [1 ]
机构
[1] Univ Munster, Inst Neurobiol, Munster, Germany
关键词
dendrite; PAR-1; pruning; Tau; SENSORY NEURONS; PROTEIN; KINASE; KATANIN; CELLS; AXON; METAMORPHOSIS; DEGENERATION; MECHANISMS; STABILITY;
D O I
10.15252/embj.201695890
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pruning of unspecific neurites is an important mechanism during neuronal morphogenesis. Drosophila 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 Drosophila. 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.
引用
收藏
页码:1981 / 1991
页数:11
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