Abstract
The centrosome, a unique membraneless multiprotein organelle, plays a pivotal role in various cellular processes that are critical for promoting cell proliferation. Faulty assembly or organization of the centrosome results in abnormal cell division, which leads to various human disorders including cancer, microcephaly and ciliopathy. Recent studies have provided new insights into the stepwise self-assembly of two pericentriolar scaffold proteins, Cep63 and Cep152, into a near-micrometre-scale higher-order structure whose architectural properties could be crucial for proper execution of its biological function. The construction of the scaffold architecture appears to be centrally required for tight control of a Ser/Thr kinase called Plk4, a key regulator of centriole duplication, which occurs precisely once per cell cycle. In this review, we will discuss a new paradigm for understanding how pericentrosomal scaffolds are self-organized into a new functional entity and how, on the resulting structural platform, Plk4 undergoes physico-chemical conversion to trigger centriole biogenesis.
Highlights
The level of intracellular Plk4 influences the ability of Plk4 to induce procentriole formation [67], suggesting that Plk4 must reach a threshold level to initiate centriole biogenesis. These results underscore the importance of tightly regulating the level of repositioned Plk4 and its subsequent activation to ensure that centriole duplication occurs precisely once per cell cycle
A growing body of evidence suggests that formation of a cylindrical Cep63-Cep152 architecture and regulation of Plk4 recruitment and function are inextricably linked
A holistic understanding of how these processes coordinately induce centriole biogenesis would require detailed investigations into the mechanisms underlying these events occurring in a 3D pericentriolar space
Summary
The centrosome composes a pair of microtubule (MT)-derived structures called centrioles and an amorphous mass of pericentriolar material (PCM) [1,2,3]. It functions as the main MT-organizing centre in animal cells and plays key roles in promoting various cellular processes, including but not limited to spindle formation, chromosome segregation and cytokinesis. The way in which PCM is organized remains largely elusive, even though a network-like ultrastructure of PCM has been visualized [9,10] This is probably because PCM is dynamically regulated throughout the cell cycle and its components are constantly turned over and replaced with those in the surrounding cytosol. The organization of inner PCM, which is thought to be more ordered than the expanded mitotic PCM in the outer region, is beginning to emerge
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