Phase separation of the Cep63•Cep152 complex underlies the formation of dynamic supramolecular self-assemblies at human centrosomes.

Cell Cycle
Jong Il AhnKyung S Lee

Abstract

The centrosome is a unique membraneless organelle that plays a pivotal role in the orderly progression of the cell cycle in animal cells. It has been shown that two pericentriolar scaffold proteins, Cep63 and Cep152, generate a heterotetrameric complex to self-assemble into a higher-order cylindrical architecture around a centriole. However, the mechanisms underlying how they reach their threshold concentrations in the vast intracellular space and generate a self-assembled architecture remain mysterious. Here we demonstrate that, like liquid-like assemblies, Cep63 and Cep152 cooperatively generate amorphous aggregates capable of undergoing dynamic turnover and inter-aggregate fusion in vivo and a significant level of internal rearrangemefnt within a condensate in vitro. Consistently, 1,6-hexanediol, a liquid-liquid phase separation disruptor, greatly diminished the ability of endogenous Cep63 and Cep152 to localize to centrosomes. Interestingly, a purified Cep63•Cep152 complex generated either a cylindrical structure or a vesicle-like hollow sphere in a spatially controlled manner. It also formed condensate-like solid spheres in the presence of a macromolecular crowder. At the molecular level, two hydrophobic motifs, one each f...Continue Reading

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Citations

May 8, 2021·Biochemical Society Transactions·Alan Wainman

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Methods Mentioned

BETA
electron microscopy
PCR
density gradient centrifugation
fluorescence recovery after photobleaching
transfection
transmission electron microscopy
electrophoresis
size-exclusion chromatography
gel
confocal microscopy

Software Mentioned

ZEN black
Imaris
Zeiss ZEN
GraphPad Prism
Zeiss
ZEN

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