Dynein light intermediate chain 1 is required for progress through the spindle assembly checkpoint
Program in Molecular Medicine; Graduate School of Biomedical Sciences, MD/PhD Program
Medical Subject Headings
Calcium-Binding Proteins; Cell Cycle Proteins; Cells, Cultured; Dynein ATPase; Hela Cells; Humans; Kinetochores; Metaphase; Mitotic Spindle Apparatus; Phosphorylation; Protein-Serine-Threonine Kinases; Repressor Proteins
The spindle assembly checkpoint monitors microtubule attachment to kinetochores and tension across sister kinetochores to ensure accurate division of chromosomes between daughter cells. Cytoplasmic dynein functions in the checkpoint, apparently by moving critical checkpoint components off kinetochores. The dynein subunit required for this function is unknown. Here we show that human cells depleted of dynein light intermediate chain 1 (LIC1) delay in metaphase with increased interkinetochore distances; dynein remains intact, localised and functional. The checkpoint proteins Mad1/2 and Zw10 localise to kinetochores under full tension, whereas BubR1 is diminished at kinetochores. Metaphase delay and increased interkinetochore distances are suppressed by depletion of Mad1, Mad2 or BubR1 or by re-expression of wtLIC1 or a Cdk1 site phosphomimetic LIC1 mutant, but not Cdk1-phosphorylation-deficient LIC1. When the checkpoint is activated by microtubule depolymerisation, Mad1/2 and BubR1 localise to kinetochores. We conclude that a Cdk1 phosphorylated form of LIC1 is required to remove Mad1/2 and Zw10 but not BubR1 from kinetochores during spindle assembly checkpoint silencing.
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Citation: EMBO J. 2009 Apr 8;28(7):902-14. Epub 2009 Feb 19. Link to article on publisher's site
Sivaram, Mylavarapu V. S.; Wadzinski, Thomas; Redick, Sambra D.; Manna, Tapas K.; and Doxsey, Stephen J., "Dynein light intermediate chain 1 is required for progress through the spindle assembly checkpoint" (2009). MD/PhD (MSTP) Program. Paper 10.