title: DSas-6 and Ana2 coassemble into tubules to promote centriole duplication and engagement.
abstract: Centrioles form cilia and centrosomes, organelles whose dysfunction is increasingly linked to human disease. Centriole duplication relies on a few conserved proteins (ZYG-1/Sak/Plk4, SAS-6, SAS-5/Ana2, and SAS-4), and is often initiated by the formation of an inner "cartwheel" structure. Here, we show that overexpressed Drosophila Sas-6 and Ana2 coassemble into extended tubules (SAStubules) that bear a striking structural resemblance to the inner cartwheel of the centriole. SAStubules specifically interact with centriole proximal ends, but extra DSas-6/Ana2 is only recruited onto centrioles when Sak/Plk4 kinase is also overexpressed. This extra centriolar DSas-6/Ana2 induces centriole overduplication and, surprisingly, increased centriole cohesion. Intriguingly, we observe tubules that are structurally similar to SAStubules linking the engaged centrioles in normal wild-type cells. We conclude that DSas-6 and Ana2 normally cooperate to drive the formation of the centriole inner cartwheel and that they promote both centriole duplication and centriole cohesion in a Sak/Plk4-dependent manner.
authors.affiliation: University of Oxford, UK.
authors.forename: Naomi R
authors.initials: NR
authors.lastname: Stevens
authors.forename: Hélio
authors.initials: H
authors.lastname: Roque
authors.forename: Jordan W
authors.initials: JW
authors.lastname: Raff
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002502:Centrioles / Q000378:metabolism* / Q000648:ultrastructure*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D015870:Gene Expression; D017344:Genes, Insect; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D055503:Protein Multimerization; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D013090:Spermatocytes / Q000378:metabolism / Q000648:ultrastructure
chemical_list: C547835:Ana2 protein, Drosophila; C539309:Asl protein, Drosophila; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C522062:Sas-6 protein, Drosophila; D017346:Protein Serine-Threonine Kinases; C522064:Sak protein, Drosophila