期刊
STRUCTURE
卷 30, 期 5, 页码 671-+出版社
CELL PRESS
DOI: 10.1016/j.str.2022.02.005
关键词
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资金
- Medical Research Council UK [MR/N009274/1]
- Cephalosporin Fund [CF 329]
- European Research Council [AdG 835322]
- European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska Curie Grant [752069]
- Marie Curie Actions (MSCA) [752069] Funding Source: Marie Curie Actions (MSCA)
Centrioles are eukaryotic organelles that play important roles in cellular processes like cilia and flagella formation, microtubule network organization, and mitotic spindle assembly. This research reveals that the asymmetric interaction mediated by the coiled-coil domain of SAS-6 is crucial for the assembly and polarity of the centriolar central scaffold, the cartwheel. Disrupting this asymmetric interaction impairs the stacking of SAS-6 rings. These findings provide new insights into the assembly of centrioles and cell division.
Centrioles are eukaryotic organelles that template the formation of cilia and flagella, as well as organize the microtubule network and the mitotic spindle in animal cells. Centrioles have proximal-distal polarity and a 9 fold radial symmetry imparted by a likewise symmetrical central scaffold, the cartwheel. The spindle assembly abnormal protein 6 (SAS-6) self-assembles into 9-fold radially symmetric ring-shaped oligomers that stack via an unknown mechanism to form the cartwheel. Here, we uncover a homo-oligomerization interaction mediated by the coiled-coil domain of SAS-6. Crystallographic structures of Chlamydomonas reinhardtii SAS-6 coiled-coil complexes suggest this interaction is asymmetric, thereby imparting polarity to the cartwheel. Using a cryoelectron microscopy (cryo-EM) reconstitution assay, we demonstrate that amino acid substitutions disrupting this asymmetric association also impair SAS-6 ring stacking. Our work raises the possibility that the asymmetric interaction inherent to SAS-6 coiled-coil provides a polar element for cartwheel assembly, which may assist the establishment of the centriolar proximal-distal axis.
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