<i>hemingway</i>is required for sperm flagella assembly and ciliary motility in<i>Drosophila</i>

Motile cilia propel directed cell movements and sweep fluids across the surface of tissues. Orthologs of Dynein Assembly Factor with WD Repeat Domains 1 (DAW1) support normal ciliary beating by enhancing delivery of dynein complexes to axonemal microtubules. DAW1 mutations in vertebrates result in multiple developmental abnormalities and early or prenatal lethality, complicating functional assessment of DAW1 in adult structures. Planarian flatworms maintain cellular homeostasis and regenerate through differentiation of adult pluripotent stem cells, and systemic RNA‐interference (RNAi) can be induced to analyze gene function at any point after birth. A single ortholog of DAW1 was identified in the genome of the planarian Schmidtea mediterranea (Smed‐daw1). Smed‐DAW1 is composed of eight WD repeats, which are 55% identical to the founding member of this protein family (Chlamydomonas reinhardtii ODA16) and 58% identical to human DAW1. Smed‐daw1 is expressed in the planarian epidermis, protonephridial excretory system, and testes, all of which contain cells functionally dependent on motile cilia. Smed‐daw1 RNAi resulted in locomotion defects and edema, which are phenotypes characteristic of multiciliated epidermis and protonephridial dysfunction, respectively. Changes in abundance or length of motile cilia were not observed at the onset of phenotypic manifestations upon Smed‐daw1 RNAi, corroborating with studies showing that DAW‐1 loss of function leads to aberrant movement of motile cilia in other organisms, rather than loss of cilia per se. However, extended RNAi treatments did result in shorter epidermal cilia and decreased abundance of ciliated protonephridia, suggesting that Smed‐daw1 is required for homeostatic maintenance of these structures in flatworms.

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“…and Thalassiosira (Table S1; Wickstead & Gull, 2007, Soulavie et al, 2014. These observations support the notion that DAW1…”

Section: Discussionsupporting

confidence: 82%

Dynein assembly factor with WD repeat domains 1 (DAW1) is required for the function of motile cilia in the planarian Schmidtea mediterranea

Lesko

Rouhana

2020

Dev Growth Differ

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“…These findings suggest that the depletion of KIAA1430 activates the spindle assembly checkpoint, thereby postponing the activation of the APC/C. Recent reports identified the ciliary protein hemingway as the Drosophila ortholog of KIAA1430 (Soulavie et al, 2014) and implicated the APC/C in regulating ciliary length and polarity (Ganner et al, 2009;Wang et al, 2014). Given that centrioles are common features of cilia and centrosomes, our data suggest that in human cells, KIAA1430 recruits a sub-fraction of the APC/C to the centrosome to facilitate mitotic progression.…”

Section: A B C Figure 2 the Stoichiometry Plotmentioning

confidence: 81%

A Human Interactome in Three Quantitative Dimensions Organized by Stoichiometries and Abundances

Hein

Hubner

Poser

et al. 2015

Cell

1,197

1,189

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The organization of a cell emerges from the interactions in protein networks. The interactome is critically dependent on the strengths of interactions and the cellular abundances of the connected proteins, both of which span orders of magnitude. However, these aspects have not yet been analyzed globally. Here, we have generated a library of HeLa cell lines expressing 1,125 GFP-tagged proteins under near-endogenous control, which we used as input for a next-generation interaction survey. Using quantitative proteomics, we detect specific interactions, estimate interaction stoichiometries, and measure cellular abundances of interacting proteins. These three quantitative dimensions reveal that the protein network is dominated by weak, substoichiometric interactions that play a pivotal role in defining network topology. The minority of stable complexes can be identified by their unique stoichiometry signature. This study provides a rich interaction dataset connecting thousands of proteins and introduces a framework for quantitative network analysis.

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“…Two putative MT-associated core proteins were also characterized: KIAA1430, the human ortholog of Drosophila hemingway (Soulavie et al, 2014), localizes to the primary cilium, while MAP7D2 localizes to cytoplasmic MT arrays in RPE-1 cells (Figure S3C). …”

Section: Resultsmentioning

confidence: 99%

A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface

Gupta

Coyaud

Gonçalves

et al. 2015

Cell

467

528

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Summary Centrioles coordinate the primary microtubule organizing center of the cell and template the formation of cilia, thereby operating at a nexus of critical cellular functions. Here we use proximity-dependent biotinylation (BioID) to map the centrosome-cilium interface; with 58 bait proteins we generate a protein topology network comprising >7000 interactions. Analysis of interaction profiles coupled with high resolution phenotypic profiling implicates a number of new protein modules in centriole duplication, ciliogenesis and centriolar satellite biogenesis, and highlights extensive interplay between these processes. By monitoring dynamic changes in the centrosome-cilium protein interaction landscape during ciliogenesis, we also identify satellite proteins that support cilia formation. Systematic profiling of proximity interactions combined with functional analysis thus provides a rich resource for better understanding human centrosome and cilia biology. Similar strategies may be applied to other complex biological structures or pathways.

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hemingwayis required for sperm flagella assembly and ciliary motility inDrosophila

Cited by 21 publications

References 44 publications

Dynein assembly factor with WD repeat domains 1 (DAW1) is required for the function of motile cilia in the planarian Schmidtea mediterranea

Dynein assembly factor with WD repeat domains 1 (DAW1) is required for the function of motile cilia in the planarian Schmidtea mediterranea

A Human Interactome in Three Quantitative Dimensions Organized by Stoichiometries and Abundances

A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface

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