Gang Dong’s group reveals a conserved mechanism for centriole targeting of Plk4 kinases


Polo-like kinase 4 has emerged as a master regulator of centriole duplication. Its central domain, the cryptic polo box, is essential to allow centriole targeting of this kinase. The findings of Gang Dong`s group at the MFPL recently published in Structure reveal the molecular mechanism for centriolar docking of the kinase, which is conserved from worms to humans.

Centrioles are – amongst other functions – essential parts of centrosomes that organize the microtubule cytoskeleton. Defects in proper centriole biogenesis often result in chromosome segregation errors and developmental disorders and have been linked with carcinogenesis.

Polo-like kinase 4 (Plk4) has been shown as a critical regulator responsible for coupling centriole duplication with cell cycle progression. It possesses a central domain known as the cryptic polo box (CPB), which is responsible for binding to the centriolar receptor proteins Asterless/Cep152 and SPD-2/Cep192 to allow centriolar targeting of Plk4. Dissecting how the CPB functions to coordinate Plk4 targeting is an essential step for our understanding about the tight control of centriole copy number.

While Plk4 is present in animals and fungi, the kinase ZYG-1 controls centriole duplication in C. elegans. It has been debated whether ZYG-1 is a bona fide homologue of Plk4 due to the low sequence similarity shared by the two kinases. In their recent paper published in Structure, which was highlighted in the August issue of the journal, Gang Dong`s group were able to show clearly the structural similarity between the CPBs of ZYG-1 and Plk4 and, by mutagenesis and in vivo studies in collaboration with Karen Oegema’s group at the University of California San Diego, to establish the molecular basis for their centriolar docking via electrostatic interactions to initiate daughter centriole assembly.

The results of Gang Dong's group not only provide compelling evidence that ZYG-1 is a Plk4 homologue in nematodes and that the mechanism for centriolar docking is conserved, but their findings also offer new information about the molecular mechanisms underlying the recruitment of Plk4 and ZYG-1 to the nascent centriole.

Original publication in Structure:
Ekaterina Shimanovskaya, Valeria Viscardi, Johannes Lesigang, Molly M. Lettman, Renping Qiao, Dmitri I. Svergun, Adam Round, Karen Oegema and Gang Dong: Structure of the C. elegans ZYG-1 Cryptic Polo Box Suggests a Conserved Mechanism for Centriolar Docking of Plk4 Kinases. In: Structure (August 2014).