Clathrin is required for the function of the mitotic spindle.

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.
Authors	Stephen J Royle, Nicholas A Bright, Leon Lagnado
Journal	Nature (Nature) Vol. 434 Issue 7037 Pg. 1152-7 (Apr 28 2005) ISSN: 1476-4687 [Electronic] England
PMID	15858577 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Autoantigens CENPB protein, human Centromere Protein B Chromosomal Proteins, Non-Histone Clathrin DNA-Binding Proteins Clathrin Heavy Chains
Topics	Animals Autoantigens (metabolism) Cell Line Centromere Protein B Chromosomal Proteins, Non-Histone (metabolism) Chromosome Segregation Clathrin (chemistry, genetics, metabolism, ultrastructure) Clathrin Heavy Chains (chemistry, genetics, metabolism, ultrastructure) DNA-Binding Proteins (metabolism) Endocytosis Humans Kinetochores (metabolism) Microscopy, Immunoelectron Mitosis Protein Structure, Tertiary Rats Spindle Apparatus (physiology, ultrastructure)

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