ZMYND10 functions in a chaperone relay during axonemal dynein assembly

Mali, Girish R.; Yeyati, Patricia L; Mizuno, Seiya; Dodd, Daniel O; Tennant, Peter; Keighren, Margaret; Lage, Petra zur; Shoemark, Amelia; García-Muñoz, Amaya; Shimada, Atsuko; Takeda, Hiroyuki; Edlich, Frank; Takahashi, Satoru; Kreigsheim, Alex von; Jarman, Andrew P.; Mill, Pleasantine

doi:10.7554/elife.34389

Cited by 49 publications

(42 citation statements)

References 61 publications

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“…Previous studies have established a strong genetic link between loss or mutation of DNAAF7 and a combined outer and inner dynein arms defect in model organisms (fly, medaka, Xenopus, mouse) and humans (PCD, CILD22) [35,36,72,73]. DNAAF7 interacts with RuvBL2 [58] and LRRC6 [35,58,74]. It was shown that the C-terminal fragment of DNAAF7 and the CS domain of LRRC6 were necessary for this interaction [35].…”

Section: Dnaafs and Their Function In Dynein Arm Assemblymentioning

confidence: 99%

“…DNAAF7 also forms complexes with C21ORF59 and DNAAF4, IDAs' dynein light chain, and components of ODAs such as TCTEX1D1 (Tctex1 domain-containing D1) and DNAI1 (Table 2) [58]. Recently, Mali and co-workers [74] revealed that, in murine cells, DNAAF7 can form a novel chaperone complex comprising DNAAF7, FKBP8, and Hsp90, which can take part in the maturation of dynein heavy chains.…”

Section: Dnaafs and Their Function In Dynein Arm Assemblymentioning

confidence: 99%

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Role of the Novel Hsp90 Co-Chaperones in Dynein Arms’ Preassembly

Fabczak

Osinka

2019

IJMS

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The outer and inner dynein arms (ODAs and IDAs) are composed of multiple subunits including dynein heavy chains possessing a motor domain. These complex structures are preassembled in the cytoplasm before being transported to the cilia. The molecular mechanism(s) controlling dynein arms’ preassembly is poorly understood. Recent evidence suggests that canonical R2TP complex, an Hsp-90 co-chaperone, in cooperation with dynein axonemal assembly factors (DNAAFs), plays a crucial role in the preassembly of ODAs and IDAs. Here, we have summarized recent data concerning the identification of novel chaperone complexes and their role in dynein arms’ preassembly and their association with primary cilia dyskinesia (PCD), a human genetic disorder.

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Section: Dnaafs and Their Function In Dynein Arm Assemblymentioning

confidence: 99%

Section: Dnaafs and Their Function In Dynein Arm Assemblymentioning

confidence: 99%

Role of the Novel Hsp90 Co-Chaperones in Dynein Arms’ Preassembly

Fabczak

Osinka

2019

IJMS

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“…Moreover, genetic ablation of the Hsp90 co-chaperone Ruvbl1/2 results in defective dynein arm assembly in zebrafish and mice (Li et al, 2017; Zhao et al, 2013). More recently, work in diverse model animals has led to a model in which DNAAFs function as part of a ‘chaperone relay,’ with distinct DNAAFs mediating specific steps in the dynein assembly process (Cho et al, 2018; Mali et al, 2018; Olcese et al, 2017; Yamaguchi et al, 2018; Zur Lage et al, 2018). Several of these studies suggest that the DNAAFs and chaperones act together in cytosolic ‘foci’ (e.g.…”

Section: Introductionmentioning

confidence: 99%

A liquid-like organelle at the root of motile ciliopathy

Huizar

Lee

Boulgakov

et al. 2018

eLife

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Motile ciliopathies are characterized by specific defects in cilia beating that result in chronic airway disease, subfertility, ectopic pregnancy, and hydrocephalus. While many patients harbor mutations in the dynein motors that drive cilia beating, the disease also results from mutations in so-called dynein axonemal assembly factors (DNAAFs) that act in the cytoplasm. The mechanisms of DNAAF action remain poorly defined. Here, we show that DNAAFs concentrate together with axonemal dyneins and chaperones into organelles that form specifically in multiciliated cells, which we term DynAPs, for dynein axonemal particles. These organelles display hallmarks of biomolecular condensates, and remarkably, DynAPs are enriched for the stress granule protein G3bp1, but not for other stress granule proteins or P-body proteins. Finally, we show that both the formation and the liquid-like behaviors of DynAPs are disrupted in a model of motile ciliopathy. These findings provide a unifying cell biological framework for a poorly understood class of human disease genes and add motile ciliopathy to the growing roster of human diseases associated with disrupted biological phase separation.

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“…Mali et al, 2018). Thus, understanding the role of RNA-associated proteins in DynAPs is an important specific challenge, while development of methods for systematic identification of RAPs from animal tissues will be broadly useful.…”

mentioning

confidence: 99%

A systematic, label-free method for identifying RNA-associated proteinsin vivoprovides insights into vertebrate ciliary beating

Drew

Lee

Cox

et al. 2020

Preprint

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Cell-type specific RNA-associated proteins (RAPs) are essential for development and homeostasis in animals. Despite a massive recent effort to systematically identify RAPs, we currently have few comprehensive rosters of cell-type specific RAPs in vertebrate tissues. Here, we demonstrate the feasibility of determining the RNA-interacting proteome of a defined vertebrate embryonic tissue using DIF-FRAC, a systematic and universal (i.e., label-free) method. Application of DIF-FRAC to cultured tissue explants of Xenopus mucociliary epithelium identified dozens of known RAPs as expected, but also several novel RAPs, including proteins related to assembly of the mitotic spindle and regulation of ciliary beating. In particular, we show that the inner dynein arm tether Cfap44 is an RNA-associated protein that localizes not only to axonemes, but also to liquid-like organelles in the cytoplasm called DynAPs. This result led us to discover that DynAPs are generally enriched for RNA. Together, these data provide a useful resource for a deeper understanding of mucociliary epithelia and demonstrate that DIF-FRAC will be broadly applicable for systematic identification of RAPs from embryonic tissues. Introduction:

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ZMYND10 functions in a chaperone relay during axonemal dynein assembly

Cited by 49 publications

References 61 publications

Role of the Novel Hsp90 Co-Chaperones in Dynein Arms’ Preassembly

Role of the Novel Hsp90 Co-Chaperones in Dynein Arms’ Preassembly

A liquid-like organelle at the root of motile ciliopathy

A systematic, label-free method for identifying RNA-associated proteinsin vivoprovides insights into vertebrate ciliary beating

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