Assessment of ciliary phenotype in primary ciliary dyskinesia by micro-optical coherence tomography

Solomon, George M.; Francis, Richard; Chu, Kengyeh K.; Birket, Susan E.; Gabriel, George C.; Trombley, John E.; Lemke, Kristi; Klena, Nikolai; Turner, Brett; Tearney, Guillermo J.; Lo, Cecilia; Rowe, Steven M.

doi:10.1172/jci.insight.91702

Cited by 32 publications

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References 45 publications

(61 reference statements)

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“…Chlamydomonas (Ahmed & Mitchell, 2005), abnormalities in angular range of cilia strokes as observed in the trachea of DAW1 mutant mice (Solomon et al, 2017), or both.…”

Section: Discussionmentioning

confidence: 99%

“…is not essential for delivery and assembly of axonemal dynein arms, but rather it seems to maximize the rate at which these occur, as loss of DAW1 activity (whether by mutation of knockdown) only leads to a reduction (and not absence) in the number of outer dynein arms assembled in axonemes of motile cilia (Ahmed & Mitchell, 2005;Gao et al, 2010;Solomon et al, 2017). Single cell RNAseq data available for planarians allows us to see whether the similar correlations are present with regards to Smed-daw1 expression at the cellular level.…”

Section: Discussionmentioning

confidence: 99%

“…Zebrafish wdr69 morpholino knockdowns develop phenotypes associated with multiple ciliopathies, including defects in organ laterality and inner ear malformation (Gao et al, 2010). In mice, mutations in Wdr69 (also known as Dynein Assembly Factor with WD Repeat Domains 1; DAW1) cause abnormalities in ciliary beating, heterotaxy, congenital heart disease, and defective mucociliary clearance (Li et al, 2015;Solomon et al, 2017). DAW1 homozygous mutant mice that develop heterotaxy die before term due to complex congenital heart defects, while those who develop situs solitus and situs inversus often (but not always) die soon after birth due to hydrocephalus (Li et al, 2015;Solomon et al, 2017) Lophotrochozoa (Newmark & Sanchez Alvarado, 2002).…”

mentioning

confidence: 99%

“…In mice, mutations in Wdr69 (also known as Dynein Assembly Factor with WD Repeat Domains 1; DAW1) cause abnormalities in ciliary beating, heterotaxy, congenital heart disease, and defective mucociliary clearance (Li et al, 2015;Solomon et al, 2017). DAW1 homozygous mutant mice that develop heterotaxy die before term due to complex congenital heart defects, while those who develop situs solitus and situs inversus often (but not always) die soon after birth due to hydrocephalus (Li et al, 2015;Solomon et al, 2017) Lophotrochozoa (Newmark & Sanchez Alvarado, 2002). These organisms have the remarkable capability of continuous cellular replenishment and regeneration of adult tissues (Pellettieri & Sanchez Alvarado, 2007;Reddien, 2018;Rink, 2013).…”

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confidence: 99%

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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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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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“…Chlamydomonas (Ahmed & Mitchell, 2005), abnormalities in angular range of cilia strokes as observed in the trachea of DAW1 mutant mice (Solomon et al, 2017), or both.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

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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“…7 The percentage of patients with PCD that exhibit situs inversus varies, but in general, it is around 50-70%. [4][5][6] Infertility is common in men with Kartagener because of impairment of sperm motility.…”

mentioning

confidence: 99%

Delayed Diagnosis of Kartagener Syndrome in a Fertile Young Man – An Unusual Case

Alduihi¹

2019

European Respiratory &Amp; Pulmonary Diseases

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Ciliary dynein arms: Cytoplasmic preassembly, intraflagellar transport, and axonemal docking

Qiu

Roy

2022

Journal Cellular Physiology

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The microtubular scaffold of motile cilia-the axoneme, is decorated with dynein arms, which are large multiprotein complexes essential for ciliary motility. Dynein arms are arranged along the length of the axoneme in a precise repeating pattern, converting chemical energy from ATP hydrolysis into ciliary mechanical movement.How these complicated molecular machines are assembled coordinately and accurately, starting from mere polypeptide chains in the cytoplasm, remains a fascinating yet perplexing question. Rapidly emerging evidence, from multiple studies carried out with different model organisms and with various methodologies, has highlighted the existence of a dedicated assembly pathway. Here, we summarize recent progress made in clarifying the axonemal dynein arm assembly process, focusing on individual assembly steps, including cytoplasmic preassembly, intraflagellar transport, and axonemal docking. K E Y W O R D S dynein arm assembly, dynein arms, motile cilia 1 | INTRODUCTION Motile cilia are microtubule-based organelles that appear as hair-like protrusions on the cell surface and are present in diverse organisms across many evolutionary lineages. The microtubule scaffold of the cilium, the axoneme, is typically organized in a unique "9 + 2" pattern, in which a pair of central microtubules is surrounded by nine peripheral microtubule doublets (each doublet comprising a complete A and an incomplete B tubule) in a circular arrangement (Figure 1) (Ishikawa et al., 2021; Ishikawa, 2017). Importantly, a variety of biological processes, ranging from the free movement of individual cells such as protozoans like Paramecium and spermatozoa to the flow of mucus over the surface of the respiratory tract and circulation of cerebrospinal fluid within the brain ventricular cavities of mammals, all depend on the coordinated beating of motile cilia (F. Zhou & Roy, 2015).Ciliary motility is imparted by molecular motors known as outer and inner dynein arms (ODAs and IDAs, respectively), which are stably attached to the surface of the A tubule of the peripheral axonemal microtubules (Figure 1) (Ishikawa et al., 2021; Ishikawa, 2017). Dynein arms are very large, complex macromolecular assemblies that consist of multiple protein subunits (the estimated size can range from 1-to 2-MDa), overall contributing for ATP catalysis, microtubule binding activity, as well as regulatory input (King, 2016). The core catalytic subunits are comprised of dynein heavy chains (HCs), which have a length of around 4500 amino acid residues (around 500 KDa in size). Additionally, HCs associate and complex with multiple intermediate chains (ICs) and light chains (LCs), forming the dynein motors. Moreover, with the help of docking complexes (DC), dynein motors are able to stably associate with the axonemal microtubules, thereby enabling sliding motion of adjacent microtubule doublets and producing the overall oscillatory movement of the axoneme.Due to their elaborate structure, absence or mutation of even a single structural component of the dynein...

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Assessment of ciliary phenotype in primary ciliary dyskinesia by micro-optical coherence tomography

Cited by 32 publications

References 45 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

Delayed Diagnosis of Kartagener Syndrome in a Fertile Young Man – An Unusual Case

Ciliary dynein arms: Cytoplasmic preassembly, intraflagellar transport, and axonemal docking

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