Abstract
Successful mitotic cell division is critically dependent on the formation of correct attachments between chromosomes and spindle microtubules. Microtubule attachments are mediated by kinetochores, which are large proteinaceous structures assembled on centromeric chromatin of mitotic chromosomes. These attachments must be sufficiently stable to transduce force; however, the strength of these attachments are also tightly regulated to ensure timely, error-free progression through mitosis. The highly conserved, kinetochore-associated NDC80 complex is a core component of the kinetochore-microtubule attachment machinery in eukaryotic cells. A small, disordered region within the Hec1 subunit of the NDC80 complex – the N-terminal “tail” domain – has been actively investigated during the last decade due to its roles in generating and regulating kinetochore-microtubule attachments. In this review, we discuss the role of the NDC80 complex, and specifically the Hec1 tail domain, at the kinetochore-microtubule interface, and how recent studies provide a more unified view of Hec1 tail domain function.
Highlights
Congression of mitotic chromosomes relies on interactions between spindle microtubules and kinetochores, which are comprised of a large number of proteins and multi-protein complexes assembled on regions of centromeric heterochromatin within each sister chromatid (Figures 1A,B)
The authors reported that while the phosphorylation state of the tail did not affect the ability of trimerized, bead-bound NDC80 complexes to track with depolymerizing microtubules in the absence of tension, when a resisting force was applied with an optical trap, phosphorylated NDC80 complexes detached from depolymerizing microtubules with significantly higher frequency than non-phosphorylated complexes (Huis in’t Veld et al, 2019). These results suggest that, at least in vitro, Hec1 tail phosphorylation affects the ability of human NDC80 complexes under tension to transduce forces from depolymerizing microtubules
One study in human cells reported a similar finding – that preventing PP1 recruitment to KNL1 compromises kinetochore-microtubule attachments (Liu et al, 2010) – two recent studies found that kinetochore-microtubule attachments and chromosome alignment were both largely unperturbed upon disruption of the PP1-KNL1 interaction (Shrestha et al, 2017; Smith et al, 2019). Consistent with these latter results, Smith et al (2019) reported no change in phosphorylation of Hec1 at kinetochores in cells in which PP1-KNL1 recruitment was perturbed. These results suggest that dephosphorylation of the Hec1 tail domain by PP1 may not be a major effector of kinetochore-microtubule attachment regulation
Summary
Congression of mitotic chromosomes relies on interactions between spindle microtubules and kinetochores, which are comprised of a large number of proteins and multi-protein complexes assembled on regions of centromeric heterochromatin within each sister chromatid (Figures 1A,B). Region – termed the Hec1 “tail” domain – plays at least two distinct roles in kinetochore function: (1) phosphorylation of the tail by the Aurora family of kinases regulates kinetochoremicrotubule attachment stability; and (2) the tail contributes to the establishment and maintenance of force-generating kinetochore-microtubule attachments in cells.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
