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Reference: Woodbury EL and Morgan DO (2007) The Role of Self-association in Fin1 Function on the Mitotic Spindle. J Biol Chem 282(44):32138-43

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Abstract


Stabilization of spindle microtubules during anaphase is essential for proper chromosome segregation (1). Fin1 is a budding yeast protein that localizes to the poles and microtubules of the spindle during anaphase and contributes to spindle stability (2,3). The N-terminal half of Fin1 is phosphorylated at multiple sites by the cyclin-dependent kinase Clb5-Cdk1, and dephosphorylation in anaphase triggers its localization to the spindle. The C-terminal half of Fin1 contains coiled-coil motifs that are required for its self-association. Here we investigated the functional importance of the two regions of Fin1. Fin1 mutants lacking the C-terminal coiled-coil domains localized to spindle pole bodies (SPBs) but not along spindle microtubules. These mutants failed to self-associate and displayed reduced binding to microtubules in vitro, but were functional in vivo and stabilized anaphase spindles when dephosphorylated. Deletion of the Fin1 C terminus suppressed the lethal phenotypes of the phospho-mutant Fin15A. Our findings suggest that the N-terminal region of Fin1 is sufficient for its regulated function as a spindle-stabilizing factor, and that this function involves association with the SPB. The ability of the C-terminal region to promote Fin1 self-association and microtubule binding may underlie the lethal effects of the deregulated Fin15A mutant.

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Journal Article
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Woodbury EL, Morgan DO
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