More isn’t always better: Limiting centrosome size in interphase

Abstract

The centrosome serves as the primary microtubule-organizing center in animal cells and, consequently, functions in many processes, such as migration and formation of the mitotic spindles. The centrosome consists of a pair of centrioles surrounded by pericentriolar material (PCM), the platform for microtubule nucleation. The pair of centrioles duplicate once per cell cycle to ensure the equal segregation of chromosomes in mitosis. The control of centrosome duplication and their capacity to nucleate microtubules is tightly coupled to cell cycle progression. Centriole duplication initiates at the beginning of the S phase and the duplicated centrioles elongate until the G2 phase. At late G2 phase, the centrosomes mature by recruiting PCM components, resulting in the increase in the microtubule-nucleating capacity that helps the formation of spindle microtubules later in mitosis. PCM recruitment in the centrosome maturation process has been intensively investigated and revealed to be regulated by mitotic kinases. However, the mechanism regulating interphase PCM recruitment remains largely unknown, especially in mammalian cells. In other organisms, centriole duplication factors, C. elegans ZYG-11 (Plk4 orthlog) and Drosophila Sas-42 (CPAP ortholog) were demonstrated to be involved in the interphase PCM recruitment. In a recent issue of Cell Cycle, Jeffery et al.3 proposed that centrosomal protein Centrobin regulates microtubule nucleation and organization by controlling the amount of PCM in interphase. Centrobin was initially identified as a daughter centriole-associated protein required for centriole duplication.4 Centrobin has been shown to have microtubule-bundling activity5 and plays a role in the stabilization of mitotic spindles by anchoring them to the centrosome,6 while the role of Centrobin in interphase cells has not been well-defined. First, Jeffery et al. showed that Centrobin is exclusively localized at centrosomes in interphase cells3 in contrast to its association with spindle microtubules during mitosis.5,6 They next showed that when Centrobin is depleted in interphase cells, the microtubules become more focused around the centrosome and sparse in the cell cortex area. Furthermore, microtubules are less stable than those in control cells, as detected by sensitivity to microtubule depolymerizing conditions and by the acetylation state of the microtubules. They further demonstrated that altered microtubule organization is caused by increase in the number of short microtubules emanating from the centrosome without changes in the microtubule dynamics. Microtubule nucleation depends on the amount and integrity of PCM proteins, and Jeffery et al. observed an increase in the intensity of PCM proteins, including γ-tubulin, AKAP450, kendrin and PCM-1 at the centrosome, while total amount of them was not affected. In summary, their data reveal a novel role for Centrobin in limiting PCM recruitment and microtubule nucleation. One interesting explanation for this function is that the presence of Centrobin at the daughter centriole is necessary to make it functionally different from the mother centriole, and in the absence of Centrobin, the daughter centriole may become more like the mother centriole, resulting in increased PCM recruitment and microtubule nucleation. Recently, it was reported that Drosophila Centrobin plays an important role in the asymmetric cell division of neuroblast in the generation of the central nervous system.7 In this case, Centrobin functions in an opposite way, although this seems to be a neuroblast-specific phenomenon; the daughter centriole harboring Centrobin can organize PCM and microtubules in interphase to anchor at the apical cortex of the neuroblast, resulting in the formation of a specific axis in the following asymmetric cell division. Further investigation of Centrobin’s function in various cellular events, including asymmetric cell division in mammalian systems, may provide valuable insights into the regulation of PCM recruitment as well as the functional difference between mother and daughter centrioles.