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Nat Cell Biol. 2016 Apr;18(4):393-403. doi: 10.1038/ncb3329. Epub 2016 Mar 21.

SAS-6 engineering reveals interdependence between cartwheel and microtubules in determining centriole architecture.

Author information

1
Laboratory of Biomolecular Research, Department of Biology and Chemistry, Paul Scherrer Institut, CH-5232 Villigen PSI, Switzerland.
2
Department of Biological Sciences, University of Tokyo, Tokyo 113-0033, Japan.
3
Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland.
4
Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule (ETH) Zürich, CH-4058 Basel, Switzerland.
5
Condensed Matter Theory Group, Paul Scherrer Institut, CH-5232 Villigen PSI, Switzerland.

Abstract

Centrioles are critical for the formation of centrosomes, cilia and flagella in eukaryotes. They are thought to assemble around a nine-fold symmetric cartwheel structure established by SAS-6 proteins. Here, we have engineered Chlamydomonas reinhardtii SAS-6-based oligomers with symmetries ranging from five- to ten-fold. Expression of a SAS-6 mutant that forms six-fold symmetric cartwheel structures in vitro resulted in cartwheels and centrioles with eight- or nine-fold symmetries in vivo. In combination with Bld10 mutants that weaken cartwheel-microtubule interactions, this SAS-6 mutant produced six- to eight-fold symmetric cartwheels. Concurrently, the microtubule wall maintained eight- and nine-fold symmetries. Expressing SAS-6 with analogous mutations in human cells resulted in nine-fold symmetric centrioles that exhibited impaired length and organization. Together, our data suggest that the self-assembly properties of SAS-6 instruct cartwheel symmetry, and lead us to propose a model in which the cartwheel and the microtubule wall assemble in an interdependent manner to establish the native architecture of centrioles.

PMID:
26999736
DOI:
10.1038/ncb3329
[Indexed for MEDLINE]

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