Strongly Truncated Dnaaf4 Plays a Conserved Role in Drosophila Ciliary Dynein Assembly as Part of an R2TP-Like Co-Chaperone Complex With Dnaaf6.
Strongly Truncated Dnaaf4 Plays a Conserved Role in Drosophila Ciliary Dynein Assembly as Part of an R2TP-Like Co-Chaperone Complex With Dnaaf6.
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强烈截断的DNAAF4在果蝇纤毛动力蛋白组装中起着保守的作用，这是与DNAAF6的R2TP样伴侣复合物的一部分。
DOI：
10.3389/fgene.2022.943197
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发表时间：
2022
影响因子：
3.7
通讯作者：
Jarman, Andrew P.
中科院分区：
文献类型：
--
作者：
Lennon, Jennifer;zur Lage, Petra;von Kriegsheim, Alex;Jarman, Andrew P.
轴丝动力蛋白马达是驱动纤毛运动的大型多亚单位复合体。这些运动复合体的细胞质组装涉及几个共伴侣，其中一些与R2TP共伴侣复合体有关。这些基因在人类中的突变会导致运动性睫毛病变，即原发性睫状肌运动障碍(PCD)，但它们的不同作用尚不完全清楚。两个这样的动力蛋白(轴丝)组装因子(DNAAFs)被认为在R2TP样复合体中共同发挥作用，它们是DNAAF4(DYX1C1)和DNAAF6(PIH1D3)。在这里，我们研究了果蝇的同源物CG14921/DNAAF4和CG5048/DNAAF6。令人惊讶的是，果蝇DNAAF4被截短，以至于它完全缺乏TPR结构域，而在人类DNAAF4中，很可能需要TPR结构域来招募HSP90。尽管如此，我们提供的证据表明，果蝇DNAAF4和DNAAF6蛋白可以结合在一个R2TP样复合体中，该复合体在动力蛋白组装中具有保守的作用。这两种基因在果蝇的两种细胞类型的发育过程中都有特异的表达和所需，这两种细胞类型分别是机械感觉节律神经元和精子。缺乏DNAAF4或DNAAF6基因的果蝇是存活的，但脉络膜神经元功能受损，缺乏能动的精子。我们提供了DNAAF4和DNAAF6是组装外动力蛋白臂(ODA)和内动力蛋白臂(IDA)子集所必需的分子证据。
Axonemal dynein motors are large multi-subunit complexes that drive ciliary movement. Cytoplasmic assembly of these motor complexes involves several co-chaperones, some of which are related to the R2TP co-chaperone complex. Mutations of these genes in humans cause the motile ciliopathy, Primary Ciliary Dyskinesia (PCD), but their different roles are not completely known. Two such dynein (axonemal) assembly factors (DNAAFs) that are thought to function together in an R2TP-like complex are DNAAF4 (DYX1C1) and DNAAF6 (PIH1D3). Here we investigate the Drosophila homologues, CG14921/Dnaaf4 and CG5048/Dnaaf6. Surprisingly, Drosophila Dnaaf4 is truncated such that it completely lacks a TPR domain, which in human DNAAF4 is likely required to recruit HSP90. Despite this, we provide evidence that Drosophila Dnaaf4 and Dnaaf6 proteins can associate in an R2TP-like complex that has a conserved role in dynein assembly. Both are specifically expressed and required during the development of the two Drosophila cell types with motile cilia: mechanosensory chordotonal neurons and sperm. Flies that lack Dnaaf4 or Dnaaf6 genes are viable but with impaired chordotonal neuron function and lack motile sperm. We provide molecular evidence that Dnaaf4 and Dnaaf6 are required for assembly of outer dynein arms (ODAs) and a subset of inner dynein arms (IDAs).
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影响因子：
14.9
作者：
Larkin A;Marygold SJ;Antonazzo G;Attrill H;Dos Santos G;Garapati PV;Goodman JL;Gramates LS;Millburn G;Strelets VB;Tabone CJ;Thurmond J;FlyBase Consortium
通讯作者：
FlyBase Consortium
影响因子：
16.6
作者：
Martino F;Pal M;Muñoz-Hernández H;Rodríguez CF;Núñez-Ramírez R;Gil-Carton D;Degliesposti G;Skehel JM;Roe SM;Prodromou C;Pearl LH;Llorca O
通讯作者：
Llorca O
影响因子：
16.6
作者：
Maurizy C;Quinternet M;Abel Y;Verheggen C;Santo PE;Bourguet M;C F Paiva A;Bragantini B;Chagot ME;Robert MC;Abeza C;Fabre P;Fort P;Vandermoere F;M F Sousa P;Rain JC;Charpentier B;Cianférani S;Bandeiras TM;Pradet-Balade B;Manival X;Bertrand E
通讯作者：
Bertrand E
DOI：
10.1073/pnas.1715915115
发表时间：
2018-02-06
影响因子：
11.1
作者：
Horani, Amjad;Ustione, Alessandro;Brody, Steven L.
通讯作者：
Brody, Steven L.
影响因子：
4.1
作者：
Chagot, Marie-Eve;Morais, Raphael Dos Santos;Quinternet, Marc
通讯作者：
Quinternet, Marc