CDK-1 inhibits meiotic spindle shortening and dynein-dependent spindle rotation in C. elegans

J Cell Biol. 2011 Jun 27;193(7):1229-44. doi: 10.1083/jcb.201104008. Epub 2011 Jun 20.

Abstract

In animals, the female meiotic spindle is positioned at the egg cortex in a perpendicular orientation to facilitate the disposal of half of the chromosomes into a polar body. In Caenorhabditis elegans, the metaphase spindle lies parallel to the cortex, dynein is dispersed on the spindle, and the dynein activators ASPM-1 and LIN-5 are concentrated at spindle poles. Anaphase-promoting complex (APC) activation results in dynein accumulation at spindle poles and dynein-dependent rotation of one spindle pole to the cortex, resulting in perpendicular orientation. To test whether the APC initiates spindle rotation through cyclin B-CDK-1 inactivation, separase activation, or degradation of an unknown dynein inhibitor, CDK-1 was inhibited with purvalanol A in metaphase-I-arrested, APC-depleted embryos. CDK-1 inhibition resulted in the accumulation of dynein at spindle poles and dynein-dependent spindle rotation without chromosome separation. These results suggest that CDK-1 blocks rotation by inhibiting dynein association with microtubules and with LIN-5-ASPM-1 at meiotic spindle poles and that the APC promotes spindle rotation by inhibiting CDK-1.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome
  • Animals
  • CDC2 Protein Kinase / antagonists & inhibitors
  • CDC2 Protein Kinase / physiology*
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / ultrastructure
  • Caenorhabditis elegans Proteins / antagonists & inhibitors
  • Caenorhabditis elegans Proteins / metabolism
  • Caenorhabditis elegans Proteins / physiology*
  • Cell Cycle Proteins / metabolism
  • Cyclin B / physiology
  • Cytoplasmic Dyneins / metabolism
  • Cytoplasmic Dyneins / physiology
  • Dyneins / physiology*
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / drug effects
  • Embryo, Nonmammalian / metabolism
  • Enzyme Inhibitors / pharmacology
  • Meiosis / physiology*
  • Microtubules / metabolism
  • Purines / pharmacology
  • Spindle Apparatus / metabolism*
  • Spindle Apparatus / ultrastructure
  • Ubiquitin-Protein Ligase Complexes / physiology

Substances

  • 6-((3-chloro)anilino)-2-(isopropyl-2-hydroxyethylamino)-9-isopropylpurine
  • Aspm-1 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • Cyclin B
  • Enzyme Inhibitors
  • Purines
  • lin-5 protein, C elegans
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • CDC2 Protein Kinase
  • Cytoplasmic Dyneins
  • DHC-1 protein, C elegans
  • Dyneins