Kinase activation of ClC-3 accelerates cytoplasmic condensation during mitotic cell rounding

Am J Physiol Cell Physiol. 2012 Feb 1;302(3):C527-38. doi: 10.1152/ajpcell.00248.2011. Epub 2011 Nov 2.

Abstract

"Mitotic cell rounding" describes the rounding of mammalian cells before dividing into two daughter cells. This shape change requires coordinated cytoskeletal contraction and changes in osmotic pressure. While considerable research has been devoted to understanding mechanisms underlying cytoskeletal contraction, little is known about how osmotic gradients are involved in cell division. Here we describe cytoplasmic condensation preceding cell division, termed "premitotic condensation" (PMC), which involves cells extruding osmotically active Cl(-) via ClC-3, a voltage-gated channel/transporter. This leads to a decrease in cytoplasmic volume during mitotic cell rounding and cell division. Using a combination of time-lapse microscopy and biophysical measurements, we demonstrate that PMC involves the activation of ClC-3 by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in human glioma cells. Knockdown of endogenous ClC-3 protein expression eliminated CaMKII-dependent Cl(-) currents in dividing cells and impeded PMC. Thus, kinase-dependent changes in Cl(-) conductance contribute to an outward osmotic pressure in dividing cells, which facilitates cytoplasmic condensation preceding cell division.

Publication types

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

MeSH terms

  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
  • Cell Cycle
  • Cell Division
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Cell Proliferation
  • Cell Shape
  • Chloride Channels / genetics
  • Chloride Channels / metabolism*
  • Chlorides
  • Cytoskeleton / metabolism
  • Gene Knockdown Techniques
  • Glioma
  • Humans
  • Mitosis*
  • Osmotic Pressure
  • Patch-Clamp Techniques

Substances

  • Chloride Channels
  • Chlorides
  • ClC-3 channel
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2