Journal
MOLECULAR CANCER
Volume 12, Issue -, Pages -Publisher
BMC
DOI: 10.1186/1476-4598-12-4
Keywords
Clathrin; Pitstop; Spindle assembly checkpoint; Metaphase; Cell death; Cancer
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Funding
- National Health and Medical Research Council (NH&MRC) of Australia
- NH&MRC Career Development Award Fellowship
- German funding agency DFG [SFB765/B4, FOR806-HA2686/3-2]
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Background: During metaphase clathrin stabilises the mitotic spindle kinetochore(K)-fibres. Many anti-mitotic compounds target microtubule dynamics. Pitstop 2 (TM) is the first small molecule inhibitor of clathrin terminal domain and inhibits clathrin-mediated endocytosis. We investigated its effects on a second function for clathrin in mitosis. Results: Pitstop 2 did not impair clathrin recruitment to the spindle but disrupted its function once stationed there. Pitstop 2 trapped HeLa cells in metaphase through loss of mitotic spindle integrity and activation of the spindle assembly checkpoint, phenocopying clathrin depletion and aurora A kinase inhibition. Conclusions: Pitstop 2 is therefore a new tool for investigating clathrin spindle dynamics. Pitstop 2 reduced viability in dividing HeLa cells, without affecting dividing non-cancerous NIH3T3 cells, suggesting that clathrin is a possible novel anti-mitotic drug target.
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