The life cycle of centrioles

Abstract

Centrioles organize the centrosome and nucleate the ciliary axoneme, and the centriole life cycle has many parallels to the chromosome cycle. The centriole cycle in animals begins at fertilization with the contribution of two centrioles by the male gamete. In the ensuing cell cycles, the duplication of centrioles is controlled temporally, spatially, and numerically. As a consequence of the duplication mechanism, the two centrioles in a typical interphase cell are of different ages and have different functions. Here, we discuss how new centrioles are assembled, what mechanisms limit centriole number, and the consequences of the inherent asymmetry of centriole duplication and segregation.

Figure 1

Vertebrate centrosome structure. Depicted is a longitudinal section of a G₂-phase mammalian centrosome. The immature procentriole is attached to its mother centriole and has an internal cartwheel structure in its proximal half. The fully mature mother centriole has two types of appendages, distal and subdistal, and lacks the cartwheel structure. Mature centriole cylinders are ~150 nm in diameter and ~400 nm long. The base of the mother centriole is embedded in the pericentriolar material, which appears in electron micrographs as darkly staining material around the centrioles.

Figure 2

Vertebrate centriole duplication cycle following only the daughter centriole. Cell cycle stages are indicated under each image. Important regulators and structural components are indicated. (A) In G₁, the daughter centriole can recruit pericentriolar material. Primary cilia are often nucleated by the mother centriole at this stage. (B) Procentriole assembly occurs during S phase, orthogonal to the base of the parental centriole, and requires Plk4 kinase activity. Structural proteins are recruited to the site of assembly before assembly of the centriolar microtubule triplets. The internal cartwheel structure appears during this stage. (C) During G₂ and M, the procentriole elongates, and the newer mother centriole (shown) acquires appendage proteins so that by mitosis, each centrosome contains one fully mature centriole and one procentriole. Note that appendages themselves have not been observed on mitotic centrioles; however, the appendage proteins remain associated with the centrioles during mitosis. (D) The mother centriole and the procentriole disengage at anaphase and become the mother and daughter centrioles. Disengagement, mediated by separase and Plk1, is a prerequisite for centriole duplication in the next cell cycle. In addition, the cartwheel structure is lost from the daughter centriole at this time.

Figure 3

Centriole functions. (A) Centrioles are required for the formation of both motile and nonmotile cilia and are often referred to as “basal bodies” in these contexts. The two types of cilia differ in their structure and functions (Dawe et al. 2007). (B) Centrioles increase the efficiency of asymmetric cell divisions and pronuclear migration. Asymmetric cell division is often mediated by the interaction of spindle microtubules with the cell cortex. In the absence of microtubule nucleation from the centrosome, cells more frequently divide symmetrically, leading to the mis-segregation of cell-fate determinants. After fertilization, the female pronucleus moves along microtubules nucleated by the sperm centrosome to meet the male pronucleus. In the absence of centrosomes, this meeting is delayed or does not occur before the first mitotic division. (C) Centrioles are not required for general mitosis, cell migration, and axon growth. Some of these processes require pericentriolar material proteins, but the organization of these proteins around a centriole is not necessary for their function.