title: DSAS-6 organizes a tube-like centriole precursor, and its absence suggests modularity in centriole assembly.
abstract: Centrioles are microtubule-based cylindrical structures that exhibit 9-fold symmetry and facilitate the organization of centrosomes, flagella, and cilia [1]. Abnormalities in centrosome structure and number occur in many cancers [1, 2]. Despite its importance, very little is known about centriole biogenesis. Recent studies in C. elegans have highlighted a group of molecules necessary for centriole assembly [1, 3]. ZYG-1 kinase recruits a complex of two coiled-coil proteins, SAS-6 and SAS-5, which are necessary to form the C. elegans centriolar tube, a scaffold in centriole formation [4, 5]. This complex also recruits SAS-4, which is required for the assembly of the centriolar microtubules that decorate that tube [4, 5]. Here we show that Drosophila SAS-6 is involved in centriole assembly and cohesion. Overexpression of DSAS-6 in syncitial embryos led to the de novo formation of multiple microtubule-organizing centers (MTOCs). Strikingly, the center of these MTOCs did not contain centrioles, as described previously for SAK/PLK4 overexpression [6]. Instead, tube-like structures were present, supporting the idea that centriolar assembly starts with the formation of a tube-like scaffold, dependent on DSAS-6 [5]. In DSAS-6 loss-of-function mutants, centrioles failed to close and to elongate the structure along all axes of the 9-fold symmetry, suggesting modularity in centriole assembly. We propose that the tube is built from nine subunits fitting together laterally and longitudinally in a modular and sequential fashion, like pieces of a layered "hollow" cake.
authors: Cancer Research UK Cell Cycle Genetics Research Group, Department of Genetics, University of Cambridge, Cambridge, UK.
authors: Ana
authors: A
authors: Rodrigues-Martins
authors: Mónica
authors: M
authors: Bettencourt-Dias
authors: Maria
authors: M
authors: Riparbelli
authors: Cláudia
authors: C
authors: Ferreira
authors: Inês
authors: I
authors: Ferreira
authors: Giuliano
authors: G
authors: Callaini
authors: David M
authors: DM
authors: Glover
mesh_terms: D000818:Animals; D002502:Centrioles / Q000378:metabolism* / Q000648:ultrastructure; D004330:Drosophila / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D008297:Male; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D009154:Mutation; D013737:Testis / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D029721:Drosophila Proteins; C522062:Sas-6 protein, Drosophila