期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-26252-5
关键词
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资金
- EMBO long-term fellowship [ALTF 820-2015]
- European Union [703907, 754510]
- Agence Nationale de la Recherche (France) [13-BSV80007-01]
- Fondation ARC pour la recherche sur le cancer [SFI20121205511]
- MINECO/FEDER [BFU2015-69275-P]
- MICINN [PGC2018-099562-B-I00]
- AGAUR [2017 SGR 1089]
- MICIU [RED2018-102723-T]
- IRB Barcelona
- Severo Ochoa Centre of Excellence Award from the Spanish Ministry of Science and Innovation
- CERCA (Generalitat de Catalunya)
- PRB3 (ISCIIISGEFI/ERDF) [IPT17/0019]
- IRB Biostatistics/Bioinformatics Core Facilility
- Animal Facility of the Parc Scientific de Barcelona
- Marie Curie Actions (MSCA) [703907] Funding Source: Marie Curie Actions (MSCA)
The study reveals that gamma TuRC in the centriole lumen plays an important role in centriole integrity and cilium assembly, and is linked to human disease.
The gamma-tubulin ring complex (gamma TuRC) nucleates microtubules at the centrosome, but how this function is related to gamma TuRC subcentrosomal distribution is unclear. Here the authors show that gamma TuRC in the centriole lumen has a nucleation-independent role in centriole integrity and cilium assembly. Centriole biogenesis and maintenance are crucial for cells to generate cilia and assemble centrosomes that function as microtubule organizing centers (MTOCs). Centriole biogenesis and MTOC function both require the microtubule nucleator gamma-tubulin ring complex (gamma TuRC). It is widely accepted that gamma TuRC nucleates microtubules from the pericentriolar material that is associated with the proximal part of centrioles. However, gamma TuRC also localizes more distally and in the centriole lumen, but the significance of these findings is unclear. Here we identify spatially and functionally distinct subpopulations of centrosomal gamma TuRC. Luminal localization is mediated by augmin, which is linked to the centriole inner scaffold through POC5. Disruption of luminal localization impairs centriole integrity and interferes with cilium assembly. Defective ciliogenesis is also observed in gamma TuRC mutant fibroblasts from a patient suffering from microcephaly with chorioretinopathy. These results identify a non-canonical role of augmin-gamma TuRC in the centriole lumen that is linked to human disease.
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