FBB18 participates in preassembly of almost all axonemal dyneins independent of R2TP complex

Wang, Limei; Li, Xuecheng; Liu, Guang; Pan, Junmin

doi:10.1371/journal.pgen.1010374

Cited by 2 publications

(1 citation statement)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Colocalization imaging in the Xenopus MCC cytoplasm shows that PF13/Ktu colocalizes with 5 different preassembly factors (ZMYND10, PIH1D3, SPAG1, LRRC6 and PF23/DYX1C1) and three chaperones (RUVBL1, RUVBL2, and HSP90) in DyNAPs [125]. In another study, co-immunoprecipitation and yeast two-hybrid assays identified that FBB18 interacts with these same three chaperones, as well as PF22, WDR92, ODA7 and PF23/DYX1C1, but not SPAG1, MOT48, RPAP3, or ZMYND10 [42,126]. PF13 and PF23 interact by immunoprecipitation [44].…”

Section: Discussionmentioning

confidence: 99%

Reduced dosage of multiple dynein arm preassembly factors limits cilia regeneration inChlamydomonas reinhardtii

Penny,

Dutcher

2023

Preprint

View full text Add to dashboard Cite

Motile cilia are complex organelles comprised of >800 structural proteins. Variants in 58 of these genes cause primary ciliary dyskinesia (PCD) in humans. We used a second-site non-complementation approach in diploidChlamydomonas reinhardtiistrains to investigate whether reduced dosage of different combinations of motile cilia proteins affects cilia growth / regeneration. Temperature-sensitive mutants in intraflagellar transport genes fail to complement in heterozygous diploids at the restrictive temperature, which may be due to poisonous interactions or a reduction in protein levels. Diploid strains heterozygous for 211 double mutant combinations in 21 genes are phenotypically recessive when unperturbed and do not show SSNC. Consequently, we developed a sensitized screen. When protein synthesis is inhibited, cells utilize the existing cytoplasmic pool of proteins, which is insufficient to build full-length cilia. Six double heterozygous strains in dynein arm preassembly factors (DNAAFs)pf13, pf23, wdr92,andoda8regrow cilia that are shorter than wild-type diploids, which suggests that double heterozygosity limits the pool of assembled dynein arms further. We isolated a new null allele (pf23-4)that shows a more severe loss of ODAs and IDAs in cilia than the previously studiedpf23-1hypomorphic allele. We also identified a new role for PF23 in cytoplasmic modification of IC138, protein of the I1/finner dynein arm. In our SSNC assay, thepf23-4allele also exhibits a more severe phenotype thanpf23-1. Whole cell extract immunoblots show a reduction of PF23 protein to one-half of wild-type levels in both single and double heterozygous genotypes. Thepf13mutant shows SSNC with mutants in two outer dynein arm structural proteins, ODA6, andODA9. We suggest that reduction of multiple dynein preassembly factors limits the pool of assembled dynein arms needed for cilia assembly and regeneration. Our data support PF23 as a scaffolding hub protein involved in dynein arm assembly.Author SummaryMotile cilia are essential for movement of cells and fluids. In humans, motile cilia defects cause primary ciliary dyskinesia (PCD), a rare disease characterized by recurring respiratory infections, left-right asymmetry defects, ear infections, and infertility. Many genes are involved in motile cilia function and assembly. We useChlamydomonas reinhardtiito study the effects of changes in protein levels in different combinations of proteins needed for motile cilia. Our results show that the proteins that help fold and assemble the dynein motors in the cytoplasm are sensitive to changes in the dosage of these preassembly factors. Reductions in proteins involved in multiple steps of the pathway prevents efficient dynein preassembly and cilia regeneration under stressful cellular conditions.

show abstract

Section: Discussionmentioning

confidence: 99%

Reduced dosage of multiple dynein arm preassembly factors limits cilia regeneration inChlamydomonas reinhardtii

Penny,

Dutcher

2023

Preprint

View full text Add to dashboard Cite

show abstract

Formation and function of multiciliated cells

Lyu,

Li,

Zhou

et al. 2023

Journal of Cell Biology

View full text Add to dashboard Cite

In vertebrates, multiciliated cells (MCCs) are terminally differentiated cells that line the airway tracts, brain ventricles, and reproductive ducts. Each MCC contains dozens to hundreds of motile cilia that beat in a synchronized manner to drive fluid flow across epithelia, the dysfunction of which is associated with a group of human diseases referred to as motile ciliopathies, such as primary cilia dyskinesia. Given the dynamic and complex process of multiciliogenesis, the biological events essential for forming multiple motile cilia are comparatively unelucidated. Thanks to advancements in genetic tools, omics technologies, and structural biology, significant progress has been achieved in the past decade in understanding the molecular mechanism underlying the regulation of multiple motile cilia formation. In this review, we discuss recent studies with ex vivo culture MCC and animal models, summarize current knowledge of multiciliogenesis, and particularly highlight recent advances and their implications.

show abstract

FBB18 participates in preassembly of almost all axonemal dyneins independent of R2TP complex

Cited by 2 publications

References 61 publications

Reduced dosage of multiple dynein arm preassembly factors limits cilia regeneration inChlamydomonas reinhardtii

Reduced dosage of multiple dynein arm preassembly factors limits cilia regeneration inChlamydomonas reinhardtii

Formation and function of multiciliated cells

Contact Info

Product

Resources

About