The versatile molecular complex component LC8 promotes several distinct steps of flagellar assembly

Gupta, Anjali; Diener, Dennis R.; Sivadas, Priyanka; Rosenbaum, Joel L.; Yang, Pinfen

doi:10.1083/jcb.201111041

Cited by 34 publications

(54 citation statements)

References 59 publications

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“…Therefore, although RSP26 is dispensable in the laboratory, it is presumably needed in Chlamydomonas' natural environment in which the temperature and nutrient availability are expected to fluctuate. Similar motility phenotypes are shown by pf25 that lacks RSP11 and partially rescued RS mutants (Gupta et al 2012).…”

Section: The Spectrum Of Motility Anomalies Of Rs Mutantssupporting

confidence: 58%

“…RSP3 is hypophosphorylated in RS precursors and in mutants with reduced RSs, such as fla14 that lacks LC8 and pf27 Gupta et al 2012), suggesting that the RSs in pf27, as in fla14, are not assembled via a normal process that involves phosphorylation. The PF27 gene has not been identified but likely encodes a protein outside of flagella .…”

Section: Rs Assemblymentioning

confidence: 99%

“…A pull-down of the spoke stalk recovered the CSC and another protein that associated with RS2, FAP206 (Gupta et al 2012). FAP206 is reduced in pf14 axonemes (Lin et al 2011).…”

Section: Rs Outer Doublet Connectionsmentioning

confidence: 99%

“…LC8 dimer, present in numerous protein complexes including multiheaded dyneins and RSs, typically brings two polypeptides in a complex together. But in RSs, a stack of LC8 dimers bring together the amino terminus of an RSP3 dimer in RS precursors to form a rod at the RS base, promoting RSP3's phosphorylation and docking to the outer doublets Gupta et al 2012). …”

Section: Rs Assemblymentioning

confidence: 99%

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Radial Spokes—A Snapshot of the Motility Regulation, Assembly, and Evolution of Cilia and Flagella

Zhu

Liu

Yang

2016

Cold Spring Harb Perspect Biol

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Section: The Spectrum Of Motility Anomalies Of Rs Mutantssupporting

confidence: 58%

Section: Rs Assemblymentioning

confidence: 99%

“…A pull-down of the spoke stalk recovered the CSC and another protein that associated with RS2, FAP206 (Gupta et al 2012). FAP206 is reduced in pf14 axonemes (Lin et al 2011).…”

Section: Rs Outer Doublet Connectionsmentioning

confidence: 99%

Section: Rs Assemblymentioning

confidence: 99%

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Radial Spokes—A Snapshot of the Motility Regulation, Assembly, and Evolution of Cilia and Flagella

Zhu

Liu

Yang

2016

Cold Spring Harb Perspect Biol

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“…49 The Dpy-30-domain-binding amphipathic helix (AH D ) has been shown to directly interact with RSP2 (the ortholog of human DYDC1) and RSP23 (the ortholog of human NME5, also named RSPH23), 50 whereas the three TQT-like domains have been found to interact directly with a LC8 (the ortholog of human DYNLL1) dimer. 51 As proposed by Sivadas et al, 50 RSP3, which is a RS-stalk protein, forms a dimer that constitutes the core of each RS and has two sites for anchoring RSP7 and RSP11 at the A-tubule of the outer-doublet side and RSP2 and RSP23 (two RS-neck proteins) at the central-pair side. In individual PCD1183, p.Gln206* (the consequence of the c.616C>T transition) is therefore expected to be highly deleterious at the protein level: mutated RSPH3 transcripts would generate a severely truncated protein lacking the six functional domains.…”

mentioning

confidence: 96%

RSPH3 Mutations Cause Primary Ciliary Dyskinesia with Central-Complex Defects and a Near Absence of Radial Spokes

Jeanson

Copin

Papon

et al. 2015

The American Journal of Human Genetics

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Primary ciliary dyskinesia (PCD) is a rare autosomal-recessive condition resulting from structural and/or functional defects of the axoneme in motile cilia and sperm flagella. The great majority of mutations identified so far involve genes whose defects result in dynein-arm anomalies. By contrast, PCD due to CC/RS defects (those in the central complex [CC] and radial spokes [RSs]), which might be difficult to diagnose, remains mostly unexplained. We identified non-ambiguous RSPH3 mutations in 5 of 48 independent families affected by CC/RS defects. RSPH3, whose ortholog in the flagellated alga Chlamydomonas reinhardtii encodes a RS-stalk protein, is mainly expressed in respiratory and testicular cells. Its protein product, which localizes within the cilia of respiratory epithelial cells, was undetectable in airway cells from an individual with RSPH3 mutations and in whom RSPH23 (a RS-neck protein) and RSPH1 and RSPH4A (RS-head proteins) were found to be still present within cilia. In the case of RSPH3 mutations, high-speed-videomicroscopy analyses revealed the coexistence of immotile cilia and motile cilia with movements of reduced amplitude. A striking feature of the ultrastructural phenotype associated with RSPH3 mutations is the near absence of detectable RSs in all cilia in combination with a variable proportion of cilia with CC defects. Overall, this study shows that RSPH3 mutations contribute to disease in more than 10% of PCD-affected individuals with CC/RS defects, thereby allowing an accurate diagnosis to be made in such cases. It also unveils the key role of RSPH3 in the proper building of RSs and the CC in humans.

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The Chlamydomonas mutant pf27 reveals novel features of ciliary radial spoke assembly

et al. 2013

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To address the mechanisms of ciliary radial spoke assembly, we took advantage of the Chlamydomonas pf27 mutant. The radial spokes that assemble in pf27 are localized to the proximal quarter of the axoneme, but otherwise are fully assembled into 20S radial spoke complexes competent to bind spokeless axonemes in vitro. Thus, pf27 is not defective in radial spoke assembly or docking to the axoneme. Rather, our results suggest that pf27 is defective in the transport of spoke complexes. During ciliary regeneration in pf27, radial spoke assembly occurs asynchronously from other axonemal components. In contrast, during ciliary regeneration in wild-type Chlamydomonas, radial spokes and other axonemal components assemble concurrently as the axoneme grows. Complementation in temporary dikaryons between wild-type and pf27 reveals rescue of radial spoke assembly that begins at the distal tip, allowing further assembly to proceed from tip to base of the axoneme. Notably, rescued assembly of radial spokes occurred independently of the established proximal radial spokes in pf27 axonemes in dikaryons. These results reveal that 20S radial spokes can assemble proximally in the pf27 cilium but as the cilium lengthens, spoke assembly requires transport. We postulate that PF27 encodes an adaptor or modifier protein required for radial spoke – IFT interaction.

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The versatile molecular complex component LC8 promotes several distinct steps of flagellar assembly

Abstract: At the tip of flagella, an array of LC8 dimers binds to the spoke protein RSP3 in radial spoke precursors, triggering phosphorylation, stalk base formation, and axoneme targeting.

Cited by 34 publications

References 59 publications

Radial Spokes—A Snapshot of the Motility Regulation, Assembly, and Evolution of Cilia and Flagella

Radial Spokes—A Snapshot of the Motility Regulation, Assembly, and Evolution of Cilia and Flagella

RSPH3 Mutations Cause Primary Ciliary Dyskinesia with Central-Complex Defects and a Near Absence of Radial Spokes

The Chlamydomonas mutant pf27 reveals novel features of ciliary radial spoke assembly

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