The Ran GTPase mediates chromatin signaling to control cortical polarity during polar body extrusion in mouse oocytes

Dev Cell. 2007 Feb;12(2):301-8. doi: 10.1016/j.devcel.2006.11.008.

Abstract

The molecular basis for asymmetric meiotic divisions in mammalian oocytes that give rise to mature eggs and polar bodies remains poorly understood. Previous studies demonstrated that the asymmetrically positioned meiotic chromosomes provide the cue for cortical polarity in mouse oocytes. Here we show that the chromatin-induced cortical response can be fully reconstituted by injecting DNA-coated beads into metaphase II-arrested eggs. The injected DNA beads induce a cortical actin cap, surrounded by a myosin II ring, in a manner that depends on the number of beads and their distance from the cortex. The Ran GTPase plays a critical role in this process, because dominant-negative and constitutively active Ran mutants disrupt DNA-induced cortical polarization. The Ran-mediated signaling to the cortex is independent of the spindle but requires cortical myosin II assembly. We hypothesize that a Ran(GTP) gradient serves as a molecular ruler to interpret the asymmetric position of the meiotic chromatin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Cell Polarity / drug effects
  • Cell Polarity / physiology*
  • Chromatin / drug effects
  • Chromatin / physiology*
  • DNA / administration & dosage
  • Enzyme Activation / drug effects
  • Female
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Mice
  • Microinjections
  • Microspheres
  • Microtubules / drug effects
  • Microtubules / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • Myosin Type II / metabolism
  • Oocytes / cytology*
  • Oocytes / drug effects
  • Oocytes / enzymology*
  • Signal Transduction* / drug effects
  • Thiazolidines / pharmacology
  • ran GTP-Binding Protein / metabolism*

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Chromatin
  • Heterocyclic Compounds, 4 or More Rings
  • Thiazolidines
  • blebbistatin
  • DNA
  • Mitogen-Activated Protein Kinases
  • Myosin Type II
  • ran GTP-Binding Protein
  • latrunculin A