Structural mechanisms for centrosomal recruitment and organization of the microtubule nucleator γ-TuRC

Qi Gao, Florian W. Hofer, Sebastian Filbeck, Bram J. A. Vermeulen, Martin Würtz, Annett Neuner, Charlotte Kaplan, Maja Zezlina, Cornelia Sala, Hyesu Shin, Oliver J. Gruss, Elmar Schiebel () and Stefan Pfeffer ()
Additional contact information
Qi Gao: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH)
Florian W. Hofer: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH)
Sebastian Filbeck: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH)
Bram J. A. Vermeulen: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH)
Martin Würtz: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH)
Annett Neuner: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH)
Charlotte Kaplan: Universität Heidelberg
Maja Zezlina: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH)
Cornelia Sala: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH)
Hyesu Shin: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH)
Oliver J. Gruss: Universität Bonn
Elmar Schiebel: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH)
Stefan Pfeffer: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH)

Nature Communications, 2025, vol. 16, issue 1, 1-23

Abstract: Abstract The γ-tubulin ring complex (γ-TuRC) acts as a structural template for microtubule formation at centrosomes, associating with two main compartments: the pericentriolar material and the centriole lumen. In the pericentriolar material, the γ-TuRC is involved in microtubule organization, while the function of the centriole lumenal pool remains unclear. The conformational landscape of the γ-TuRC, which is crucial for its activity, and its centrosomal anchoring mechanisms, which determine γ-TuRC activity and turnover, are not understood. Using cryo-electron tomography, we analyze γ-TuRCs in human cells and purified centrosomes. Pericentriolar γ-TuRCs simultaneously associate with the essential adapter NEDD1 and the microcephaly protein CDK5RAP2. NEDD1 forms a tetrameric structure at the γ-TuRC base through interactions with four GCP3/MZT1 modules and GCP5/6-specific extensions, while multiple copies of CDK5RAP2 engage the γ-TuRC in two distinct binding patterns to promote γ-TuRC closure and activation. In the centriole lumen, the microtubule branching factor Augmin tethers a condensed cluster of γ-TuRCs to the centriole wall with defined directional orientation. Centriole-lumenal γ-TuRC-Augmin is protected from degradation during interphase and released in mitosis to aid chromosome alignment. This study provides a unique view on γ-TuRC structure and molecular organization at centrosomes and identifies an important cellular function of centriole-lumenal γ-TuRCs.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-57729-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57729-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-57729-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().