Removal of Spindly from microtubule-attached kinetochores controls spindle checkpoint silencing in human cells

Genes & Development
Reto GassmannArshad Desai

Abstract

The spindle checkpoint generates a "wait anaphase" signal at unattached kinetochores to prevent premature anaphase onset. Kinetochore-localized dynein is thought to silence the checkpoint by transporting checkpoint proteins from microtubule-attached kinetochores to spindle poles. Throughout metazoans, dynein recruitment to kinetochores requires the protein Spindly. Here, we identify a conserved motif in Spindly that is essential for kinetochore targeting of dynein. Spindly motif mutants, expressed following depletion of endogenous Spindly, target normally to kinetochores but prevent dynein recruitment. Spindly depletion and Spindly motif mutants, despite their similar effects on kinetochore dynein, have opposite consequences on chromosome alignment and checkpoint silencing. Spindly depletion delays chromosome alignment, but Spindly motif mutants ameliorate this defect, indicating that Spindly has a dynein recruitment-independent role in alignment. In Spindly depletions, the checkpoint is silenced following delayed alignment by a kinetochore dynein-independent mechanism. In contrast, Spindly motif mutants are retained on microtubule-attached kinetochores along with checkpoint proteins, resulting in persistent checkpoint signalin...Continue Reading

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Related Concepts

Dynein Activity
Microtubule-Associated Protein 3
Spindle Checkpoint Silencing
Mitotic Anaphase
Thyroid Hormone Plasma Membrane Transport Defect
Genes, cdc
Microtubules
Protein Structure, Supersecondary
Spindle Poles
Spindly protein, human

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