Clathrin is required for the function of the mitotic spindle

Stephen J. Royle (), Nicholas A. Bright and Leon Lagnado
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Stephen J. Royle: MRC Laboratory of Molecular Biology
Nicholas A. Bright: University of Cambridge, Addenbrooke's Hospital
Leon Lagnado: MRC Laboratory of Molecular Biology

Nature, 2005, vol. 434, issue 7037, 1152-1157

Abstract: Abstract Clathrin has an established function in the generation of vesicles that transfer membrane and proteins around the cell1,2,3,4. The formation of clathrin-coated vesicles occurs continuously in non-dividing cells5, but is shut down during mitosis6, when clathrin concentrates at the spindle apparatus7,8. Here, we show that clathrin stabilizes fibres of the mitotic spindle to aid congression of chromosomes. Clathrin bound to the spindle directly by the amino-terminal domain of clathrin heavy chain. Depletion of clathrin heavy chain using RNA interference prolonged mitosis; kinetochore fibres were destabilized, leading to defective congression of chromosomes to the metaphase plate and persistent activation of the spindle checkpoint. Normal mitosis was rescued by clathrin triskelia but not the N-terminal domain of clathrin heavy chain, indicating that stabilization of kinetochore fibres was dependent on the unique structure of clathrin. The importance of clathrin for normal mitosis may be relevant to understanding human cancers that involve gene fusions of clathrin heavy chain.

Date: 2005
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DOI: 10.1038/nature03502

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