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Abstract:
Mitotic cells face the challenging tasks of linking kinetochores to
growing and, shortening microtubules and actively regulating these
dynamic attachments to produce accurate chromosome segregation. We
report here that Ndc80/Hec1 functions in regulating kinetochore
microtubule plus-end dynamics and attachment stability. Microinjection
of an antibody to the N terminus of Hec1 suppresses both microtubule
detachment and microtubule plus-end polymerization and depolymerization
at kinetochores of PtK1 cells. Centromeres become hyperstretched,
kinetochore fibers shorten from spindle poles, kinetochore microtubule
attachment errors increase, and chromosomes severely mis-segregate. The
N terminus of Hec1 is phosphorylated by Aurora B kinase in vitro, and
cells expressing N-terminal nonphosphorylatable mutants of Hec1 exhibit
an increase in merotelic attachments, hyperstretching of centromeres,
and errors in chromosome segregation. These findings reveal a key role
for the Hec1 N terminus in controlling dynamic behavior of kinetochore
microtubules.
