Ciliary dynein motor preassembly is regulated by Wdr92 in association with HSP90 co-chaperone, R2TP.
Ciliary dynein motor preassembly is regulated by Wdr92 in association with HSP90 co-chaperone, R2TP.
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DOI：
10.1083/jcb.201709026
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发表时间：
2018-07-02
期刊：
影响因子：
--
通讯作者：
Jarman AP
中科院分区：
文献类型：
--
作者：
Zur Lage P;Stefanopoulou P;Styczynska-Soczka K;Quinn N;Mali G;von Kriegsheim A;Mill P;Jarman AP
Wdr92与多功能辅伴侣R2TP相关，但其功能尚不清楚。在这项研究中，作者发现，果蝇Wdr92是纤毛动力蛋白运动复合体预组装所必需的，该复合体仅限于感觉神经元、纤毛树突和精子鞭毛。Wdr92被认为引导R2TP/HSP90到动力素链客户端的伴侣细胞质预组装。驱动纤毛和鞭毛运动的大量动力蛋白运动复合体需要细胞质预组装，这一过程需要专门的动力蛋白组装因子(DNAAFs)。DNAAFs如何与分子伴侣相互作用来控制动力蛋白组装尚不清楚。通过与著名的多功能HSP90相关辅伴侣R2TP的类比，一些DNAAFs被建议执行新的R2TP样功能。然而，R2TP本身(典型的R2TP)对动力蛋白组装的参与仍不清楚。在这里，我们证明了在果蝇中，R2TP相关因子Wdr92是轴丝动力蛋白组装所必需的，可能与典型的R2TP有关。蛋白质组学分析表明，除了作为R2TP伴侣活性的调节器外，Wdr92还与DNAAF Spag1一起在动力蛋白预组装的不同阶段工作。Wdr92/R2TP的功能可能与DNAAFs的功能不同，DNAAFs的功能可能与DNAAFs形成动力蛋白特异的R2TP样复合体的功能不同。因此，我们的发现建立了动力蛋白组装和核心多功能辅伴侣之间的联系。
Wdr92 is associated with the multifunctional cochaperone, R2TP, but its function is unknown. In this study, the authors show that Drosophila Wdr92 is exclusively required for preassembly of ciliary dynein motor complexes, which are confined to sensory neuron ciliary dendrites and sperm flagella. Wdr92 is proposed to direct R2TP/HSP90 to dynein chain clients to chaperone cytoplasmic preassembly. The massive dynein motor complexes that drive ciliary and flagellar motility require cytoplasmic preassembly, a process requiring dedicated dynein assembly factors (DNAAFs). How DNAAFs interact with molecular chaperones to control dynein assembly is not clear. By analogy with the well-known multifunctional HSP90-associated cochaperone, R2TP, several DNAAFs have been suggested to perform novel R2TP-like functions. However, the involvement of R2TP itself (canonical R2TP) in dynein assembly remains unclear. Here we show that in Drosophila melanogaster, the R2TP-associated factor, Wdr92, is required exclusively for axonemal dynein assembly, likely in association with canonical R2TP. Proteomic analyses suggest that in addition to being a regulator of R2TP chaperoning activity, Wdr92 works with the DNAAF Spag1 at a distinct stage in dynein preassembly. Wdr92/R2TP function is likely distinct from that of the DNAAFs proposed to form dynein-specific R2TP-like complexes. Our findings thus establish a connection between dynein assembly and a core multifunctional cochaperone.
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影响因子：
4.5
作者：
Mirón-García MC;Garrido-Godino AI;García-Molinero V;Hernández-Torres F;Rodríguez-Navarro S;Navarro F
通讯作者：
Navarro F
影响因子：
9.9
作者：
通讯作者：
--
影响因子：
3.3
作者：
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通讯作者：
Eberl, Daniel F.
影响因子：
4.5
作者：
Diggle CP;Moore DJ;Mali G;zur Lage P;Ait-Lounis A;Schmidts M;Shoemark A;Garcia Munoz A;Halachev MR;Gautier P;Yeyati PL;Bonthron DT;Carr IM;Hayward B;Markham AF;Hope JE;von Kriegsheim A;Mitchison HM;Jackson IJ;Durand B;Reith W;Sheridan E;Jarman AP;Mill P
通讯作者：
Mill P
影响因子：
2.9
作者：
Liang, Xin;Madrid, Johnson;Saleh, Henri S.;Howard, Jonathon
通讯作者：
Howard, Jonathon