Loss of KLP-19 polar ejection force causes misorientation and missegregation of holocentric chromosomes

J Cell Biol. 2004 Sep 27;166(7):991-1001. doi: 10.1083/jcb.200403036.

Abstract

Holocentric chromosomes assemble kinetochores along their length instead of at a focused spot. The elongated expanse of an individual holocentric kinetochore and its potential flexibility heighten the risk of stable attachment to microtubules from both poles of the mitotic spindle (merotelic attachment), and hence aberrant segregation of chromosomes. Little is known about the mechanisms that holocentric species have evolved to avoid this type of error. Our studies of the influence of KLP-19, an essential microtubule motor, on the behavior of holocentric Caenorhabditis elegans chromosomes suggest that it has a major role in combating merotelic attachments. Depletion of KLP-19, which associates with nonkinetochore chromatin, allows aberrant poleward chromosome motion during prometaphase, misalignment of holocentric kinetochores, and multiple anaphase chromosome bridges in all mitotic divisions. Time-lapse movies of GFP-labeled mono- and bipolar spindles demonstrate that KLP-19 generates a force on relatively stiff holocentric chromosomes that pushes them away from poles. We hypothesize that this polar ejection force minimizes merotelic misattachment by maintaining a constant tension on pole-kinetochore connections throughout prometaphase, tension that compels sister kinetochores to face directly toward opposite poles.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Polarity / genetics*
  • Chromatin / genetics
  • Chromatin / metabolism
  • Chromosome Segregation / genetics*
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / metabolism
  • Kinesins / genetics
  • Kinesins / metabolism*
  • Kinetochores / metabolism
  • Kinetochores / ultrastructure
  • Microtubules / genetics
  • Microtubules / metabolism
  • Mitosis / genetics*
  • Molecular Motor Proteins / genetics
  • Molecular Motor Proteins / metabolism
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Chromatin
  • KLP-19 protein, C elegans
  • Molecular Motor Proteins
  • Kinesins