Format

Send to

Choose Destination
Curr Biol. 2017 Jun 5;27(11):1692-1699.e3. doi: 10.1016/j.cub.2017.04.058. Epub 2017 May 25.

Hec1 Tail Phosphorylation Differentially Regulates Mammalian Kinetochore Coupling to Polymerizing and Depolymerizing Microtubules.

Author information

1
Tetrad Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA.
2
Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA; MCB Graduate Program, University of Washington, Seattle, WA 98195, USA.
3
Tetrad Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Cell and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: sophie.dumont@ucsf.edu.

Abstract

The kinetochore links chromosomes to dynamic spindle microtubules and drives both chromosome congression and segregation. To do so, the kinetochore must hold on to depolymerizing and polymerizing microtubules. At metaphase, one sister kinetochore couples to depolymerizing microtubules, pulling its sister along polymerizing microtubules [1, 2]. Distinct kinetochore-microtubule interfaces mediate these behaviors: active interfaces transduce microtubule depolymerization into mechanical work, and passive interfaces generate friction as the kinetochore moves along microtubules [3, 4]. Despite a growing understanding of the molecular components that mediate kinetochore binding [5-7], we do not know how kinetochores physically interact with polymerizing versus depolymerizing microtubule bundles, and whether they use the same mechanisms and regulation to do so. To address this question, we focus on the mechanical role of the essential load-bearing protein Hec1 [8-11] in mammalian cells. Hec1's affinity for microtubules is regulated by Aurora B phosphorylation on its N-terminal tail [12-15], but its role at the interface with polymerizing versus depolymerizing microtubules remains unclear. Here we use laser ablation to trigger cellular pulling on mutant kinetochores and decouple sisters in vivo, and thereby separately probe Hec1's role on polymerizing versus depolymerizing microtubules. We show that Hec1 tail phosphorylation tunes friction along polymerizing microtubules and yet does not compromise the kinetochore's ability to grip depolymerizing microtubules. Together, the data suggest that kinetochore regulation has differential effects on engagement with growing and shrinking microtubules. Through this mechanism, the kinetochore can modulate its grip on microtubules over mitosis and yet retain its ability to couple to microtubules powering chromosome movement.

KEYWORDS:

Hec1; Ndc80; force generation; friction; kinetochore; kinetochore-microtubule interface; mechanics; microtubule; mitosis; spindle

PMID:
28552353
PMCID:
PMC5502739
DOI:
10.1016/j.cub.2017.04.058
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center