Dendrite arborization requires the dynein cofactor NudE.

Dendrite arborization requires the dynein cofactor NudE.
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DOI:
10.1242/jcs.170316
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发表时间:
2015-06-01
影响因子:
4
通讯作者:
Wildonger J
Wildonger J
中科院分区:
生物学2区
文献类型:
--
作者:
Arthur AL;Yang SZ;Abellaneda AM;Wildonger J

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基于微管的分子运动动力蛋白对于适当的神经元形态发生是必不可少的。动力蛋白活性受辅因子调节,这些辅因子在塑造神经元结构中的作用仍在阐明中。使用果蝇,我们揭示了动力蛋白辅因子NudE的损失导致异常树突树枝化。我们的数据表明,NudE与高尔基前哨,介导树突分支,表明NudE通常影响树突图案通过调节高尔基前哨运输。缺乏NudE的神经元也增加了微管动力学,反映了微管稳定性的变化,这可能也有助于异常树突生长和分支。树突状细胞发生中的这些缺陷是通过提高Lis 1的水平来挽救的,Lis 1是另一种动力蛋白辅因子,作为三方复合物的一部分与NudE相互作用。我们的数据进一步表明,NudE的C-末端是树突形态发生,并可能调节NudE活性。我们提出,NudE的一个关键功能是增强Lis 1和动力蛋白之间的相互作用,这对运动活动和树突结构至关重要。
The microtubule-based molecular motor dynein is essential for proper neuronal morphogenesis. Dynein activity is regulated by cofactors, and the role(s) of these cofactors in shaping neuronal structure are still being elucidated. Using Drosophila melanogaster, we reveal that the loss of the dynein cofactor NudE results in abnormal dendrite arborization. Our data show that NudE associates with Golgi outposts, which mediate dendrite branching, suggesting that NudE normally influences dendrite patterning by regulating Golgi outpost transport. Neurons lacking NudE also have increased microtubule dynamics, reflecting a change in microtubule stability that is likely to also contribute to abnormal dendrite growth and branching. These defects in dendritogenesis are rescued by elevating levels of Lis1, another dynein cofactor that interacts with NudE as part of a tripartite complex. Our data further show that the NudE C-terminus is dispensable for dendrite morphogenesis and is likely to modulate NudE activity. We propose that a key function of NudE is to enhance an interaction between Lis1 and dynein that is crucial for motor activity and dendrite architecture.
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