UC San Diego
Molecular mechanisms of centriole assembly
- Author(s): Lettman, Molly Marie
- et al.
Centrioles function in the recruitment of pericentriolar material proteins to form centrosomes, the main microtubule organizing centers of animal cells, and in templating the formation of cilia, which are important for many sensory, motility, and signaling functions. Centrioles are cylindrical organelles comprised of a structure termed the cartwheel, which contains a ̃25 nm central hub and nine-fold symmetric spokes emanating outward, and an outer wall of stabilized microtubules, which are also nine-fold symmetric. Regulation of centriole assembly, such that it occurs precisely once per cell cycle, is critical to maintain the correct number of centrosomes and thus bipolar spindle formation. Aberrant centriole number results in a loss of chromosome segregation fidelity. Additionally, structural defects in centrioles lead to defective cilia and are one of the underlying causes of a class of diseases called ciliopathies. In the last decade, many of the genes involved in centriole assembly have been identified and the precise roles of these genes in the process of centriole assembly are beginning to be elucidated. SAS-6 is the main structural component of the centriolar cartwheel. The work presented here uncouples, for the first time, the localization of SAS-6 to the site of new centriole assembly from its incorporation into the cartwheel. Investigation into these proceses identified three distinct regions of SAS-6 that are required for its localization to the site of new centriole assembly. Additional studies showed that, contrary to previous reports, SAS-6 is likely not the target of the critical kinase ZYG-1. These discoveries have implications on the mechanisms limiting centriole assembly to once per cell cycle