Moonlighting of mitotic regulators in cilium disassembly

Cenna Doornbos,Ronald Roepman

doi:10.1007/s00018-021-03827-5

Abstract

Correct timing of cellular processes is essential during embryological development and to maintain the balance between healthy proliferation and tumour formation. Assembly and disassembly of the primary cilium, the cell’s sensory signalling organelle, are linked to cell cycle timing in the same manner as spindle pole assembly and chromosome segregation. Mitotic processes, ciliary assembly, and ciliary disassembly depend on the centrioles as microtubule-organizing centres (MTOC) to regulate polymerizing and depolymerizing microtubules. Subsequently, other functional protein modules are gathered to potentiate specific protein–protein interactions. In this review, we show that a significant subset of key mitotic regulator proteins is moonlighting at the cilium, among which PLK1, AURKA, CDC20, and their regulators. Although ciliary assembly defects are linked to a variety of ciliopathies, ciliary disassembly defects are more often linked to brain development and tumour formation. Acquiring a better understanding of the overlap in regulators of ciliary disassembly and mitosis is essential in finding therapeutic targets for the different diseases and types of tumours associated with these regulators.

Highlights

Primary cilia are small organelles protruding from the plasma membrane
If we look at the structural conservation between the cilia and kinetochores, we can see that the further you go towards the outside of the kinetochores, the more proteins you will find that play a role in ciliary disassembly (Fig. 3b)
It would be interesting to see if MAD2L, BUB3, BUB1 and the RZZ have a similar mechanism of regulating BUB1B and CDC20 in ciliary disassembly by determining the exact spatiotemporal positions of these interactors

Summary

Introduction

Primary cilia are small organelles protruding from the plasma membrane. Their immobility distinguishes them from their motile counterparts, that have a clear function in extracellular fluid propulsion. The exact ciliary signalling functions of the primary cilia vary widely and depend on the developmental stage and cell type. Due to their near-ubiquitous prevalence, dysfunction of the cilia can disturb the formation and functioning of a variety of organs, and is linked to a wide, overlapping spectrum of hereditary disorders denominated “ciliopathies” [7]. This link is best explained by the important double role of the centrosomal centrioles in both segregation of the sister chromatids during cell division and in ciliogenesis during the G0/G1 phase of the cells cycle (Fig. 1a). The mother centriole docks to the plasma membrane using the distal appendages and drive the accumulation of ciliogenesis-specific proteins towards the pericentriolar matrix (PCM) to form the basal body, from

C Basal body

Conclusion