Centriolar cap proteins CP110 and CPAP control slow elongation of microtubule plus ends

DOI: 10.1083/jcb.202406061

Authors: Saishree S. Iyer (Utrecht University) , Fangrui Chen (Utrecht University) , Funso E. Ogunmolu (Utrecht University) , Shoeib Moradi (Paul Scherrer Institut) , Vladimir A. Volkov (Utrecht University; Delft University of Technology) , Emma J. Van Grinsven (Utrecht University) , Chris Van Hoorn (Utrecht University) , Jingchao Wu (Utrecht University) , Nemo Andrea (Delft University of Technology) , Shasha Hua (Utrecht University) , Kai Jiang (Utrecht University) , Ioannis Vakonakis (University of Oxford) , Mia Potočnjak (Ludwig-Maximilians-Universität München) , Franz Herzog (Ludwig-Maximilians-Universität München) , Benoît Gigant (CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay) , Nikita Gudimchuk (Russian Academy of Sciences, Lomonosov Moscow State University) , Kelly E. Stecker (Utrecht University; Netherlands Proteomics Cente) , Marileen Dogterom (Delft University of Technology) , Michel O. Steinmetz (Paul Scherrer Institute; University of Basel) , Anna Akhmanova (Utrecht University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Cell Biology , VOL 224

State: Published (Approved)
Published: March 2025
Diamond Proposal Number(s): 21035

Abstract: Centrioles are microtubule-based organelles required for the formation of centrosomes and cilia. Centriolar microtubules, unlike their cytosolic counterparts, are stable and grow very slowly, but the underlying mechanisms are poorly understood. Here, we reconstituted in vitro the interplay between the proteins that cap distal centriole ends and control their elongation: CP110, CEP97, and CPAP/SAS-4. We found that whereas CEP97 does not bind to microtubules directly, CP110 autonomously binds microtubule plus ends, blocks their growth, and inhibits depolymerization. Cryo-electron tomography revealed that CP110 associates with the luminal side of microtubule plus ends and suppresses protofilament flaring. CP110 directly interacts with CPAP, which acts as a microtubule polymerase that overcomes CP110-induced growth inhibition. Together, the two proteins impose extremely slow processive microtubule growth. Disruption of CP110–CPAP interaction in cells inhibits centriole elongation and increases incidence of centriole defects. Our findings reveal how two centriolar cap proteins with opposing activities regulate microtubule plus-end elongation and explain their antagonistic relationship during centriole formation.

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: B21-High Throughput SAXS

Added On: 27/01/2025 09:39

Discipline Tags:

Biochemistry Chemistry Structural biology Biophysics Life Sciences & Biotech

Technical Tags:

Scattering Small Angle X-ray Scattering (SAXS)