Centriole growth is limited by the Cdk/Cyclin-dependent phosphorylation of Ana2/STIL

Author:

Steinacker Thomas L.1ORCID,Wong Siu-Shing1ORCID,Novak Zsofia A.1,Saurya Saroj1ORCID,Gartenmann Lisa1ORCID,van Houtum Eline J.H.1ORCID,Sayers Judith R.1ORCID,Lagerholm B. Christoffer2ORCID,Raff Jordan W.1ORCID

Affiliation:

1. Sir William Dunn School of Pathology, University of Oxford, Oxford, UK 1

2. Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK 2

Abstract

Centrioles duplicate once per cell cycle, but it is unclear how daughter centrioles assemble at the right time and place and grow to the right size. Here, we show that in Drosophila embryos the cytoplasmic concentrations of the key centriole assembly proteins Asl, Plk4, Ana2, Sas-6, and Sas-4 are low, but remain constant throughout the assembly process—indicating that none of them are limiting for centriole assembly. The cytoplasmic diffusion rate of Ana2/STIL, however, increased significantly toward the end of S-phase as Cdk/Cyclin activity in the embryo increased. A mutant form of Ana2 that cannot be phosphorylated by Cdk/Cyclins did not exhibit this diffusion change and allowed daughter centrioles to grow for an extended period. Thus, the Cdk/Cyclin-dependent phosphorylation of Ana2 seems to reduce the efficiency of daughter centriole assembly toward the end of S-phase. This helps to ensure that daughter centrioles stop growing at the correct time, and presumably also helps to explain why centrioles cannot duplicate during mitosis.

Funder

Wellcome Trust

Cancer Research UK

Balliol Jason Hu Scholarship

Clarendon Scholarship

Medical Research Council

Publisher

Rockefeller University Press

Subject

Cell Biology

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