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Centrosome function and assembly inanimal cells
Paul T.Conduit1, Alan Wainman2 and Jordan W.Raff2
Abstract | It has become clear that the role of centrosomes extends well beyond that of important microtubule organizers. There is increasing evidence that they also function as coordination centres in eukaryotic cells, at which specific cytoplasmic proteins interact at high concentrations and important cell decisions are made. Accordingly, hundreds of proteins are concentrated at centrosomes, including cell cycle regulators, checkpoint proteins and signalling molecules. Nevertheless, several observations have raised the question of whether centrosomes are essential for many cell processes. Recent findings have shed light on the functions of centrosomes in animal cells and on the molecular mechanisms of centrosome assembly, in particular during mitosis. These advances should ultimately allow the invitro reconstitution of functional centrosomes from their component proteins to unlock the secrets of these enigmatic organelles.
As their name implies, centrosomes have long been thought to have a central role in many aspects of cell organization14. More than a hundred years ago, it was recognized that centrosomes form the two poles of the bipolar mitotic spindle, which separates chromosomes to daughter cells during animal cell division. If embryos from certain species were induced to assemble too many centrosomes, multipolar spindles could form, leading to the mis-segregation of chromosomes and usually embryo death. However, some embryos survived for long enough to develop into abnormal monsters, prompting Boveri to famously speculate that the disturbance to home ostasis resulting from such chromosome imbalance might predispos e cells to malignant transformation5.
We now know that centrosomes contain a pair of centrioles at their core, each having a ninefold symmetric structure (BOX1). In animal cells, the centrioles exhibit a complex behaviour during the cell cycle, often forming a cilium in quiescent cells and a centrosome in pro liferating cells (FIG.1). Cilia have many important functions in cells, and their dysfunction has been linked to many human pathologies; this subject has been reviewed extensively elsewhere68. Centrosomes are formed when centrioles assemble and organize a matrix of peri
centriolar material (PCM) around themselves
(FIG.1). The PCM contains hundreds of proteins9,10, including important cell cycle regulators and signalling molecules4, and many proteins that help to organize and nucleate microtubules, explaining...