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primary topic: Structural and functional mechanisms for centrosomal organization of γ-tubulin ring complex

Structural and functional mechanisms for centrosomal organization of γ-tubulin ring complex
type: Article
abstract: Microtubules are key components of the cytoskeleton, playing essential roles in cellular processes such as division and migration. In vivo, microtubule assembly begins with nucleation, a process typically mediated by γ-TuRCs. These complexes act as structural templates that guide the spatial and temporal polymerization of α/β-tubulin dimers, a function crucial for organizing microtubule networks at MTOCs, including the centrosome in human somatic cells. Recent advances in cryo-EM have provided high-resolution structural insights into purified γ-TuRCs, revealing their asymmetric, ring-shaped architecture and the arrangement of core subunits. These studies have deepened our understanding of γ-TuRC structure, assembly, and potential activation mechanisms. However, key questions remain about their native organization within centrosomes—specifically, their spatial distribution, interactions with targeting and activation factors, and regulation during the cell cycle and mitosis. In this study, cryo-ET was used to visualize human centrosomes and uncover the in situ structure and molecular organization of γ-TuRCs. Two distinct centrosomal pools of γ-TuRCs were identified: one located in the PCM and another within the centriole lumen. In the PCM, γ-TuRCs are often associated with the adaptor protein NEDD1 and the activator CDK5RAP2. NEDD1 forms a tetrameric structure at the γ-TuRC cone region through interactions with GCP3/MZT1 modules and GCP5/6 extensions. Its binding to the centrosomin (CM1) motif of CDK5RAP2 occurs in distinct patterns that correlate with conformational changes in γ-TuRCs. Within the centriole lumen, γ-TuRCs form a compact, highly organized cluster tethered to the centriole wall via the Augmin complex, which interacts with the inner centriolar protein POC5. These lumenal γ-TuRC–Augmin assemblies are shielded from degradation during interphase and are released at the onset of mitosis to promote spindle formation. This study reveals that centrosomal γ-TuRC…
date: 2025
author list: authors
type: EPrint
type: DoctoralThesisEPrint
is part of: repository
has document: Structural and functional mechanisms for centrosomal organization of γ-tubulin ring complex (PDF)
has document: Structural and functional mechanisms for centrosomal organization of γ-tubulin ring complex (Other)
subject: 570 Biowissenschaften, Biologie

Structural and functional mechanisms for centrosomal organization of γ-tubulin ring complex (PDF)
type: Document
has file: PhD Thesis Qi Gao.pdf
has part: PhD Thesis Qi Gao.pdf

Qi Gao
type: Person
given name: Qi
family name: Gao

Structural and functional mechanisms for centrosomal organization of γ-tubulin ring complex (Other)
type: Document
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Structural and functional mechanisms for centrosomal organization of γ-tubulin ring complex (Other)
type: Document
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Structural and functional mechanisms for centrosomal organization of γ-tubulin ring complex (Other)
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Structural and functional mechanisms for centrosomal organization of γ-tubulin ring complex (Other)
type: Document
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Structural and functional mechanisms for centrosomal organization of γ-tubulin ring complex (Other)
type: Document
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primary topic: Structural and functional mechanisms for centrosomal organization of γ-tubulin ring complex

570 Biowissenschaften, Biologie
type: Concept
preferred label: 570 Life sciences @en