A role for Tctex-1 (DYNLT1) in controlling primary cilium length.

A role for Tctex-1 (DYNLT1) in controlling primary cilium length.
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DOI:
10.1016/j.ejcb.2011.05.003
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发表时间:
2011-10
影响因子:
6.6
通讯作者:
Stephens, David J.
Stephens, David J.
中科院分区:
生物学3区
文献类型:
--
作者:
Palmer, Krysten J.;MacCarthy-Morrogh, Lucy;Smyllie, Nicola;Stephens, David J.
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已知的微管运动复合体胞浆动力蛋白参与多种过程,包括膜组织和运输、有丝分裂和微管组织。大多数关于细胞质动力蛋白的研究都集中在围绕动力蛋白-1重链构建的发动机的形式上。第二个亚型Dynein Heavy Chain-2及其特异结合的轻质中间链LIC3(D2LIC)参与了初生纤毛的形成和功能。我们在人类上皮细胞中使用RNAi来定义与初级纤毛中的动力蛋白重链2一起发挥作用的细胞质动力蛋白亚基。我们发现动力蛋白轻链Tctex-1是纤毛长度控制的关键调节器;Tctex-1的耗尽导致纤毛更长,这一点由轴丝的乙酰化微管蛋白标记和纤毛膜的Rab8a标记所定义。动力蛋白重链-2的抑制会导致Tctex-1的伴随丢失,这与纤毛长度的增加有关。与单独缺失相比,dhC2和Tctex-1的双重siRNA缺失导致纤毛长度的增加更大。我们的数据显示,Tctex-1是纤毛长度的关键调节因子,很可能是Dynein-2的一部分。
The microtubule motor complex cytoplasmic dynein is known to be involved in multiple processes including endomembrane organization and trafficking, mitosis, and microtubule organization. The majority of studies of cytoplasmic dynein have focussed on the form of the motor that is built around the dynein-1 heavy chain. A second isoform, dynein heavy chain-2, and its specifically associated light intermediate chain, LIC3 (D2LIC), are known to be involved in the formation and function of primary cilia. We have used RNAi in human epithelial cells to define the cytoplasmic dynein subunits that function with dynein heavy chain 2 in primary cilia. We identify the dynein light chain Tctex-1 as a key modulator of cilia length control; depletion of Tctex-1 results in longer cilia as defined by both acetylated tubulin labelling of the axoneme and Rab8a labelling of the cilia membrane. Suppression of dynein heavy chain-2 causes concomitant loss of Tctex-1 and this correlates with an increase in cilia length. Compared to individual depletions, double siRNA depletion of DHC2 and Tctex-1 causes an even greater increase in cilia length. Our data show that Tctex-1 is a key regulator of cilia length and most likely functions as part of dynein-2.
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细胞质动力蛋白术语。
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