Structural Basis of the 9-Fold Symmetry of Centrioles

Daiju Kitagawa,Ioannis Vakonakis,Natacha Olieric,Manuel Hilbert,Debora Keller,Vincent Olieric,Miriam Bortfeld,Michèle C Erat,Isabelle Flückiger,Pierre Gönczy,Michel O Steinmetz

doi:10.1016/j.cell.2011.01.008

Daiju Kitagawa, Ioannis Vakonakis + Show 9 more

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https://doi.org/10.1016/j.cell.2011.01.008

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Abstract

SummaryThe centriole, and the related basal body, is an ancient organelle characterized by a universal 9-fold radial symmetry and is critical for generating cilia, flagella, and centrosomes. The mechanisms directing centriole formation are incompletely understood and represent a fundamental open question in biology. Here, we demonstrate that the centriolar protein SAS-6 forms rod-shaped homodimers that interact through their N-terminal domains to form oligomers. We establish that such oligomerization is essential for centriole formation in C. elegans and human cells. We further generate a structural model of the related protein Bld12p from C. reinhardtii, in which nine homodimers assemble into a ring from which nine coiled-coil rods radiate outward. Moreover, we demonstrate that recombinant Bld12p self-assembles into structures akin to the central hub of the cartwheel, which serves as a scaffold for centriole formation. Overall, our findings establish a structural basis for the universal 9-fold symmetry of centrioles.

Highlights

Centrioles are fundamental for the assembly of cilia and flagella across eukaryotic evolution
Structural and Biophysical Characterization of C. elegans SAS-6 We first set out to characterize the structure of C. elegans SAS-6 to uncover the mechanisms by which it contributes to centriole formation
Full-length SAS-6 and C. elegans SAS-6 (ceN)-CC were decorated with a globular head-like moiety at one end (Figure 1B, arrowheads), which is absent in ceCC, indicating that it corresponded to the N-terminal domain of SAS-6

Summary

Introduction

Centrioles are fundamental for the assembly of cilia and flagella across eukaryotic evolution (reviewed in Azimzadeh and Marshall, 2010). Centrioles are important for assembling the centrosome, the major microtubule organizing center (MTOC) of animal cells, and as such, they are critical for genome stability. As anticipated from these important roles, aberrations in centriole structure or function are implicated in a number of disease conditions, including ciliopathies, male sterility, primary microcephaly, and cancer (reviewed in Nigg and Raff, 2009). Centrioles, and the related basal bodies, are barrel-shaped microtubule-containing structures characterized by a universal 9-fold radial symmetry that they impart to cilia and flagella (reviewed in Azimzadeh and Marshall, 2010). The molecular and structural principles directing the universal 9-fold symmetry of the cartwheel and the centriole remain to be discovered

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