Centrosomes as signalling centres

Abstract

Centrosomes-as well as the related spindle pole bodies (SPBs) of yeast-have been extensively studied from the perspective of their microtubule-organizing roles. Moreover, the biogenesis and duplication of these organelles have been the subject of much attention, and the importance of centrosomes and the centriole-ciliary apparatus for human disease is well recognized. Much less developed is our understanding of another facet of centrosomes and SPBs, namely their possible role as signalling centres. Yet, many signalling components, including kinases and phosphatases, have been associated with centrosomes and spindle poles, giving rise to the hypothesis that these organelles might serve as hubs for the integration and coordination of signalling pathways. In this review, we discuss a number of selected studies that bear on this notion. We cover different processes (cell cycle control, development, DNA damage response) and organisms (yeast, invertebrates and vertebrates), but have made no attempt to be comprehensive. This field is still young and although the concept of centrosomes and SPBs as signalling centres is attractive, it remains primarily a concept-in need of further scrutiny. We hope that this review will stimulate thought and experimentation.

Keywords: DNA damage; cell cycle; centrosome; mitosis; signalling hub; spindle pole body.

Figure 1.

Centrosomes as signalling centres. It is well established that centrosomes (and SPBs) respond to multiple external signals (a). Increasing attention is being devoted to the alternative scenario, where centrosomes (and SPBs) function as signalling centres and solid-state platforms to influence cell physiology (b). The evolutionary advantages of using centrosomes (and SPBs) to locally concentrate signalling proteins could be manifold, as described in the main text. (c) Emphasizes the integration of multiple signalling pathways, the enhanced kinetics of biochemical reactions and the build-up of concentration gradients. (Online version in colour.)

Figure 2.

Activation of Cdk1/cyclin complexes at the fission yeast SPB. (a) General scheme of Cdk1/cyclin B activation at the G2/M transition. (b,c) Role of fission yeast SPB-component Cut12 in the assembly of components involved in the activation of Cdk1 at the G2/M transition. For details, see text and [36]. (Online version in colour.)

Figure 3.

Centrosomes promote the onset of NEBD in the C. elegans one-cell embryo. The scheme depicts the role of centrosomes in facilitating NEBD in the C. elegans one-cell embryo (light grey/red, female pronucleus; dark grey/blue, male pronucleus; dashed black line, NEBD; filled black line, intact pronuclear membrane; black/green dots, centrosomes), as described in [67,68]. Light/red and dark grey/blue bars refer to the timing of NEBD for the female and male pronucleus, respectively. (a) The situations are described for wild-type embryos, (b) embryos with a defect in pronuclear migration, (c) centrosome integrity, (d) a centrosome attachment defect and (e) embryos depleted of Aurora A. (Online version in colour.)