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PreprintCited by 42Microtubule and mitosis dynamicsGenetic and Kidney Cyst DiseasesCancer Treatment and Pharmacology

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CSPP1 stabilizes growing microtubule ends and damaged lattices from the luminal side

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van den Berg, Cyntha M., Volkov, Vladimir A., Schnorrenberg, Sebastian, Huang, Ziqiang, Stecker, Kelly E., Grigoriev, Ilya, Patzke, Sebastian, Zimmermann, Timo, Dogterom, Marileen, Akhmanova, Anna·2022·The Journal of Cell Biology
DOI 10.1101/2022.06.23.497320PMC PMC9948759

Preprint — published as 10.1083/jcb.202208062

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Abstract

Microtubules are dynamic cytoskeletal polymers, and their organization and stability are tightly regulated by numerous cellular factors. While regulatory proteins controlling formation of interphase microtubule arrays and mitotic spindles have been extensively studied, the biochemical mechanisms responsible for generating stable microtubule cores of centrioles and cilia are poorly understood. Here, we used in vitro reconstitution assays to investigate microtubule-stabilizing properties of CSPP1, a centrosome and cilia-associated protein mutated in the neurodevelopmental ciliopathy Joubert syndrome. We found that CSPP1 preferentially binds to polymerizing microtubule ends that grow slowly or undergo growth perturbations and, in this way, resembles microtubule-stabilizing compounds such as taxanes. Fluorescence microscopy and cryo-electron tomography showed that CSPP1 is deposited in the microtubule lumen and inhibits microtubule growth and shortening through two separate domains. CSPP1 also specifically recognizes and stabilizes damaged microtubule lattices. These data help to explain how CSPP1 regulates elongation and stability of ciliary axonemes and other microtubule-based structures.

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Metadata

Authors
van den Berg, C. M., Volkov, V. A., Schnorrenberg, S., Huang, Z., Stecker, K. E., Grigoriev, I., Patzke, S., Zimmermann, T., Dogterom, M., & Akhmanova, A.
Affiliations
  • Utrecht University (NL)
  • European Molecular Biology Laboratory (DE)
  • Oslo University Hospital (NO)
  • Delft University of Technology (NL)
Corresponding author
Akhmanova, Anna
ORCID
Venue
The Journal of Cell Biology
Publisher
openRxiv
Published
2022-06-25
Volume
222
Issue
4
ISSN
0021-9525 (ISSN-L)
DOI
10.1101/2022.06.23.497320
PMC
PMC9948759
OpenAlex
W4319461548
Cited by
42
References
1
Citations by year
2026: 9 · 2025: 15 · 2024: 11 · 2023: 6 · 2022: 1
FWCI
5.93
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • The Journal of Cell Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • Research Repository (Delft University of Technology) (submittedVersion, cc-by)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders
  • Kreftforeningen
  • Queen Mary University of London (SBC8VOL2)
  • European Molecular Biology Laboratory
  • ZonMw (TOP 91216006, 91216006)
  • Technische Universiteit Delft
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (711.018.004)
  • Boehringer Ingelheim Stiftung
  • European Research Council (609822)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
Keywords
microtubule stabilization, microtubule ends, ciliary axoneme, centrioles, Joubert syndrome, ciliopathies
MeSH terms
Abnormalities, Multiple, Centrioles, Cerebellum, Cytoskeleton, Eye Abnormalities, Humans, Microtubule-Associated Proteins, Microtubules, Retina, Centrosome, Cell Cycle Proteins, Kidney Diseases, Cystic

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