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PMID:15858577

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Citation

Royle, SJ, Bright, NA and Lagnado, L (2005) Clathrin is required for the function of the mitotic spindle. Nature 434:1152-7

Abstract

Clathrin has an established function in the generation of vesicles that transfer membrane and proteins around the cell. The formation of clathrin-coated vesicles occurs continuously in non-dividing cells, but is shut down during mitosis, when clathrin concentrates at the spindle apparatus. 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.

Links

PubMed Online version:10.1038/nature03502

Keywords

Animals; Autoantigens/metabolism; Cell Line; Centromere Protein B; Chromosomal Proteins, Non-Histone/metabolism; Chromosome Segregation; Clathrin/chemistry; Clathrin/genetics; Clathrin/metabolism; Clathrin/ultrastructure; Clathrin Heavy Chains/chemistry; Clathrin Heavy Chains/genetics; Clathrin Heavy Chains/metabolism; Clathrin Heavy Chains/ultrastructure; DNA-Binding Proteins/metabolism; Endocytosis; Humans; Kinetochores/metabolism; Microscopy, Immunoelectron; Mitosis; Mitotic Spindle Apparatus/physiology; Mitotic Spindle Apparatus/ultrastructure; Protein Structure, Tertiary; Rats

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:CLH1

involved_in

GO:0000278: mitotic cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:CLH1

located_in

GO:0005819: spindle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:CLH1

involved_in

GO:0006898: receptor-mediated endocytosis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CLH1

located_in

GO:0005819: spindle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CLH1

involved_in

GO:0000278: mitotic cell cycle

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CLH1

involved_in

GO:0006898: receptor-mediated endocytosis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CLH1

part_of

GO:0005819: spindle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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