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Article
Spatial control of microtubule length and lifetime by opposing stabilizing and destabilizing functions of Kinesin-8
Current Biology (2014)
  • Yusuke Fukuda, The University of Chicago
  • Anna Luchniak, The University of Chicago
  • Erin R. Murphy, The University of Chicago
  • Mohan L. Gupta, Jr., The University of Chicago
Abstract
Background—To function in diverse cellular processes, the dynamic behavior of microtubules
(MTs) must be differentially regulated within the cell. In budding yeast, the spindle position
checkpoint (SPOC) inhibits mitotic exit in response to mispositioned spindles. To maintain SPOCmediated
anaphase arrest, astral MTs must maintain persistent interactions with and/or extend
through the bud neck. However, the molecular mechanisms that ensure the stability of these
interactions are not known.
Results—The presence of a MT extending through and/or interacting with the bud neck is
maintained by spatial control of catastrophe and rescue, which extends MT lifetime >25-fold and
controls the length of dynamic MTs within the bud compartment. Moreover, the single kinesin-8
motor, Kip3, alternately mediates both catastrophe and rescue of the bud MT. Kip3 accumulates in
a length-dependent manner along the lattice of MTs within the bud. Yet, it induces catastrophe
spatially near the bud tip. Rather, this accumulation of Kip3 facilitates its association with
depolymerizing MT plus-ends, where Kip3 promotes rescue before MTs exit the bud. MT rescue
within the bud requires the tail domain of Kip3, whereas the motor domain mediates catastrophe at
the bud tip. In vitro, Kip3 exerts both stabilizing and destabilizing effects on reconstituted yeast
MTs.
Conclusions—The kinesin-8 Kip3 is a multifunctional regulator that differentially stabilizes and
destabilizes specific MTs. Control over MT catastrophe and rescue by Kip3 defines the length and
lifetime of MTs within the bud compartment of cells with mispositioned spindles. This subcellular
regulation of MT dynamics is critical to maintain mitotic arrest in response to mispositioned
spindles.
Publication Date
August 18, 2014
DOI
10.1016/j.cub.2014.06.069
Publisher Statement
© 2014 Elsevier Ltd
Citation Information
Yusuke Fukuda, Anna Luchniak, Erin R. Murphy and Mohan L. Gupta. "Spatial control of microtubule length and lifetime by opposing stabilizing and destabilizing functions of Kinesin-8" Current Biology Vol. 24 Iss. 16 (2014) p. 1826 - 1835
Available at: http://works.bepress.com/mohan-gupta/14/