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.

Once and only once: mechanisms of centriole duplication and their deregulation in disease

“…Each centrosome typically comprises a pair of centrioles, which assemble a protein matrix, the pericentriolar material (PCM). The PCM harbors not only proteins important for microtubule nucleation 5 , but also regulators of the cell cycle and its checkpoints, in line with important roles for centrosomes in intracellular signaling 6 . Fully mature centrioles can also dock at the plasma membrane where they function as basal bodies for the formation of cilia and flagella 7 , and dysfunction of the basal body-ciliary apparatus gives rise to ciliopathies 8 .…”

The PLK4–STIL–SAS-6 module at the core of centriole duplication

“…By influencing microtubule distribution as well as dynamics [1], centrosomes are important for a variety of cellular processes, including cell motility, shape, polarity and division, as well as intracellular signaling (reviewed in refs [2–4]). Each centrosome comprises a pair of centrioles, surrounded by pericentriolar material (PCM) [5].…”

Cell polarity: having and making sense of direction—on the evolutionary significance of the primary cilium/centrosome organ in Metazoa

“…126, 138): ‘Cilia mediate an astonishing diversity of processes … the logic of this combinatorial signalling represents one of the most important challenges to the ciliogenesis field … the cellular “antenna”, far from being a passive receiver of input signals, is due for an upgrade to the status of a cellular “central processing unit”, and perhaps the main one integrating extracellular signalling with the cell cycle and metabolism.’ Is there any specific role of the basal body itself for such a quite important function? A similar function—as hub for signalling integration and cell cycle control—has been proposed for the centrosome [206]. Analysis of the evolution of the interactions at the centriole–basal body transition should bring key informations [216,217].…”