CoChat
Sign Up
PreprintCited by 6Genetic and Kidney Cyst DiseasesCystic Fibrosis Research AdvancesMicrotubule and mitosis dynamics

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

DNAAF9 (Shulin) and ARL3 regulate the transport and activation of ciliary Outer Dynein Arms (ODAs)

Open access
Issa, Karim Housseini B, Ren, Muyang, Burnet, Bradley, Melia, Charlotte, Heesom, Kate, Mali, Girish R.·2024·Nature Structural & Molecular Biology
DOI 10.1101/2024.08.15.608058PMC PMC12700831

Preprint — published as 10.1038/s41594-025-01680-9 · Paper page

Open this paper in CoChat — free account

Abstract

Multiciliogenesis requires large-scale biosynthesis of motility-powering axonemal inner and outer dynein arm motors (IDA and ODA) prior to their intraflagellar transport (IFT) into cilia. ODAs are inhibited by the packaging chaperone Shulin during ciliogenesis in T. thermophila. How Shulin is released for ODAs to become active inside cilia remains unclear. We establish interactions between DNAAF9 (human Shulin) and mammalian ODA subunits, IFT proteins and the ciliary small GTPase ARL3 using proteomics and in vitro reconstitutions. Mutagenesis combined with biochemical and structural studies reveal that DNAAF9 and Shulin preferentially bind the active Arl3-GTP state. GTP-loaded Arl3 can access, bind and displace Shulin from the packaged ODA-Shulin complex. We propose that once the inhibited ODA complex enters growing cilia, Arl3-GTP displaces Shulin (DNAAF9) and sequesters it away from ODAs promoting activation of their motility specifically inside cilia.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/2024.08.15.608058

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 41

  1. 10.1093/biosci/biu180 · DOI
  2. Wallmeier, J. et al. Motile ciliopathies . Nat. Rev. Dis. Prim. 6, (2020). · DOI · Paper page
  3. 10.1002/cm.970290304 · DOI
  4. 10.1091/mbc.E18-05-0291 · DOI
  5. 10.1083/jcb.200608041 · DOI
  6. 10.1083/jcb.200802025 · DOI
  7. 10.1016/S0021-9258(17)32121-X · DOI
  8. 10.1126/science.abe0526 · DOI
  9. 10.1038/s41594-019-0286-y · DOI
  10. 10.1080/21541248.2016.1224454 · DOI
  11. Travis, A. M. et al. Disrupting the ciliary gradient of active Arl3 affects rod photoreceptor nuclear migration. Elife 12, (2023). · DOI
  12. 10.1016/j.ajhg.2018.08.015 · DOI
  13. 10.1101/gad.173443.111 · DOI
  14. 10.1093/hmg/ddx143 · DOI
  15. 10.1165/rcmb.2017-0436OC · DOI
  16. Walton, T. et al. Axonemal structures reveal mechanoregulatory and disease mechanisms. Nature 618, 625 (2023). · DOI
  17. 10.1021/acs.jproteome.6b00972 · DOI
  18. Kubo, S. et al. Remodeling and activation mechanisms of outer arm dyneins revealed by cryo-EM. EMBO Rep. 22, (2021). · DOI
  19. 10.1083/jcb.200912001 · DOI
  20. Gotthardt, K. et al. A G-protein activation cascade from Arl13B to Arl3 and implications for ciliary targeting of lipidated proteins. Elife 4, (2015). · DOI
  21. 10.7554/eLife.62047 · DOI
  22. 10.1038/nsmb.1396 · DOI
  23. 2015, The Interaction of CCDC104/BARTL1 with Arl3 and Implications for Ciliary Function, Struct. England1993), 23, 2122, 10.1016/j.str.2015.08.016 · DOI
  24. 10.2353/ajpath.2006.050941 · DOI
  25. 10.1093/hmg/ddx143 · DOI
  26. 2018, Binary Function of ARL3-GTP Revealed by Gene Knockouts, Adv. Exp. Med. Biol, 1074, 317, 10.1007/978-3-319-75402-4_39 · DOI
  27. 2000, LdARL-3A, a Leishmania promastigote-specific ADP-ribosylation factor-like protein, is essential for flagellum integrity, J. Cell Sci, 113, 2065, 10.1242/jcs.113.11.2065 · DOI
  28. 10.1101/2023.04.12.536397 · DOI
  29. 10.1038/nmeth.2019 · DOI · Paper page
  30. 10.1038/nmeth.2557 · DOI · Paper page
  31. 10.1093/BIOINFORMATICS/BTZ931 · DOI · Paper page
  32. 10.1038/nmeth.4330 · DOI
  33. 1991, Purification and characterization of dynein from pig tracheal cilia, Methods Enzymol, 196, 223, 10.1016/0076-6879(91)96021-I · DOI
  34. 10.1038/S41592-022-01488-1 · DOI · Paper page
  35. 2024, Accurate structure prediction of biomolecular interactions with AlphaFold 3, Nat, 630, 493, 10.1038/s41586-024-07487-w · DOI · Paper page
  36. Bittrich, S. , Segura, J. , Duarte, J. M. , Burley, S. K. & Rose, Y . RCSB protein Data Bank: exploring protein 3D similarities via comprehensive structural alignments. Bioinformatics 40, (2024). · DOI
  37. 10.1002/pro.3235 · DOI · Paper page
  38. 10.1093/bioinformatics/btm404 · DOI
  39. 10.1093/nar/gkg556 · DOI
  40. 10.1093/nar/gkw408 · DOI · Paper page
  41. 10.1093/NAR/GKAB1038 · DOI · Paper page

Metadata

Authors
Issa, K. H. B., Ren, M., Burnet, B., Melia, C., Heesom, K., & Mali, G. R.
Affiliations
  • University of Oxford (GB)
  • University of Bristol (GB)
Corresponding author
Mali, Girish R.
ORCID
Venue
Nature Structural & Molecular Biology
Publisher
openRxiv
Published
2024-08-16
Volume
32
Issue
12
Pages
2454-2464
ISSN
1545-9985 (ISSN-L)
DOI
10.1101/2024.08.15.608058
PMC
PMC12700831
OpenAlex
W4414589064
Cited by
6
References
1
Citations by year
2026: 3 · 2025: 3
FWCI
3.53
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Structural & Molecular Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • Bristol Research (University of Bristol) (submittedVersion, cc-by)
  • Explore Bristol Research (submittedVersion, cc-by)
Funders
  • Wellcome Trust
  • Academy of Medical Sciences (SBF007\1001)
  • Medical Research Council (MR/X007219/1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Keywords
outer dynein arm, cilia, ciliogenesis, intraflagellar transport, axoneme, Tetrahymena thermophila, GTP binding, ciliary motility
MeSH terms
Animals, Cilia, Dyneins, Guanosine Triphosphate, Humans, Models, Molecular, Protein Binding, Tetrahymena thermophila, Molecular Chaperones, ADP-Ribosylation Factors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review