FBB18 participates in preassembly of almost all axonemal dyneins independent of R2TP complex.
FBB18 participates in preassembly of almost all axonemal dyneins independent of R2TP complex.
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DOI：
10.1371/journal.pgen.1010374
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发表时间：
2022-08
期刊：
影响因子：
4.5
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中科院分区：
文献类型：
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动力蛋白臂的组装需要由动力蛋白预组装因子（DNAAFs）介导的细胞质过程。CFAP 298在具有运动纤毛的生物体中是保守的，是动力蛋白臂组装所需的，但机制不清楚。在这里，我们表明，FBB 18，CFAP 298的衣原体同源物，定位于细胞质和功能的折叠/稳定的几乎所有轴丝动力蛋白在早期步骤的动力蛋白预组装。FBB 18基因突变导致纤毛缺失或变短，并伴有动力蛋白外臂和内臂的部分缺失。使用15 N标记的比较蛋白质组学表明，几乎所有的轴丝动力蛋白重链（DHCs）的部分降解。模拟患者变异体的突变体诱导DHCα的特定丢失。FBB 18与9个DNAAF和15个动力蛋白HC中的14个相关，但不与IC 1/IC 2相关。FBB 18与RuvBL 1/2相互作用，RuvBL 1/2是HSP 90共伴侣R2 TP复合物的组分，但不与holo-R2 TP复合物相互作用。进一步的分析表明，同时形成多个DNAAF复合物涉及动力蛋白折叠/稳定性，从而提供了新的见解轴丝动力蛋白预组装。运动纤毛对人类生理学是重要的，纤毛运动的缺陷可能导致人类疾病，如男性不育和原发性纤毛运动障碍。纤毛的运动需要轴丝动力蛋白的预组装。使用遗传和其他方法的组合，我们研究了FBB 18的工作机制，CFAP 298的衣原体同源物，缺陷导致原发性纤毛运动障碍。我们发现FBB 18参与细胞质中的动力蛋白折叠/稳定性，这与其在纤毛内动力蛋白复合物的纤毛靶向或动力蛋白臂的稳定中的功能不同。此外，我们还提供了证据表明，多个不同的复合物同时形成参与动力蛋白折叠，从而提供了新的见解动力蛋白预组装。最后但并非最不重要的是，我们表明，RuvBL 1/2的HSP 90共伴侣R2 TP复合物可能独立的R2 TP复合物在动力蛋白拆卸。这项工作具有科学和医学意义，并将普遍关注纤毛生物学和蛋白质折叠/稳定性领域。
Assembly of dynein arms requires cytoplasmic processes which are mediated by dynein preassembly factors (DNAAFs). CFAP298, which is conserved in organisms with motile cilia, is required for assembly of dynein arms but with obscure mechanisms. Here, we show that FBB18, a Chlamydomonas homologue of CFAP298, localizes to the cytoplasm and functions in folding/stabilization of almost all axonemal dyneins at the early steps of dynein preassembly. Mutation of FBB18 causes no or short cilia accompanied with partial loss of both outer and inner dynein arms. Comparative proteomics using 15N labeling suggests partial degradation of almost all axonemal dynein heavy chains (DHCs). A mutant mimicking a patient variant induces particular loss of DHCα. FBB18 associates with 9 DNAAFs and 14 out of 15 dynein HCs but not with IC1/IC2. FBB18 interacts with RuvBL1/2, components of the HSP90 co-chaperone R2TP complex but not the holo-R2TP complex. Further analysis suggests simultaneous formation of multiple DNAAF complexes involves dynein folding/stability and thus provides new insights into axonemal dynein preassembly. Motile cilia are important for human physiology and defects in cilia motility may cause human disorders such as male infertility and primary ciliary dyskinesia. The motility of cilia requires preassembly of axonemal dyneins. Using a combination of genetic and other approaches, we have studied the working mechanism of FBB18, a Chlamydomonas homologue of CFAP298, defects in which result in primary ciliary dyskinesia. We found that FBB18 participates in dynein folding/stability in the cytoplasm, which is distinct from its proposed function in ciliary targeting of dynein complexes or stabilization of dynein arms within cilia. In addition, we have provided evidence that multiple distinct complexes are simultaneously formed to participate in dynein folding, thus providing new insights into dynein preassembly. Last but not least, we showed that RuvBL1/2 of the HSP90 co-chaperone R2TP complex may function independently of the R2TP complex in dynein disassembly. This work has both scientific and medical significance and will be of general interest to the fields of ciliary biology and protein folding/stability.
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DOI：
10.1083/jcb.112.3.441
发表时间：
1991-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kamiya R;Kurimoto E;Muto E
通讯作者：
Muto E
影响因子：
3.3
作者：
Dean, Anudariya B.;Mitchell, David R.
通讯作者：
Mitchell, David R.
影响因子：
9.8
作者：
Hoeben, Inga M.;Hjeij, Rim;Omran, Heymut
通讯作者：
Omran, Heymut
影响因子：
9.8
作者：
Austin-Tse, Christina;Halbritter, Jan;Hildebrandt, Friedhelm
通讯作者：
Hildebrandt, Friedhelm
DOI：
10.1083/jcb.201006105
发表时间：
2010-09-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Craige B;Tsao CC;Diener DR;Hou Y;Lechtreck KF;Rosenbaum JL;Witman GB
通讯作者：
Witman GB