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Protein phosphorylation-mediated control of centriole growth

Published in the Journal of Cell Biology, work by the Raff lab uncovers a key new mechanism mediated by protein phosphorylation that regulates centriole growth and duplication during the cell cycle.

The cell cycle is a highly regulated cellular process required for tissue development and homeostasis, whose dysregulation is associated with cancer. Centrioles are microtubule-based organelles involved in the control of cell division via the formation of centrosomes. Centriole number is therefore tightly regulated and the formation of a new centriole can occur only next to a pre-existing centriole. Centriole duplication is known to take place specifically during the cell cycle phase of DNA replication (S-phase). However, it remains unclear how daughter centrioles grow to the correct size and how centriole duplication is restricted to S-phase.

Jordan Raff’s group have investigated whether the cytoplasmic concentration of core centriole duplication proteins are changing during the nuclear cycle, which could explain how centriole’s growth is regulated. However, the authors found that while the cytoplasmic concentration of the centriole duplication proteins is low, their concentration remains constant through the centrioles assembly. Interestingly, the authors observed that the cytoplasmic diffusion rate of one of the centriole duplication protein, Ana2, increases towards the end of S-phase and depends partially on the phosphorylation of Ana2 by the cell cycle kinase Cdk1/Cyclin activity. In addition, phosphorylation of Ana2 also inhibits its ability to promote centriole duplication. As Cdk1/cyclin activity increases toward mitosis, these observations provide a mechanism on how centriole growth and duplication is constrained to S-phase.

Written by Michael Tellier (Murphy lab) @Michael_Tellier

Edited by Isabella Maudlin (Murphy lab) @BellaMaudlin

Thomas L. Steinacker*, Siu-Shing Wong*, Zsofia A. Novak, Saroj Saurya, Lisa Gartenmann, Eline J.H. van Houtum, Judith R. Sayers, B. Christoffer Lagerholm, Jordan W. Raff (2022). Centriole growth is limited by the Cdk/Cyclin-dependent phosphorylation of Ana2/STIL. Journal of Cell Biology, 221 (9) e202205058.