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

Vishnu Anand Cuddapah, Christa W. Habela, Stacey Watkins, Lindsay S. Moore, T. T.C. Barclay, Harald Sontheimer

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


"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 voltagegated 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.

Original languageEnglish (US)
Pages (from-to)C527-C538
JournalAmerican Journal of Physiology - Cell Physiology
Issue number3
StatePublished - Feb 2012
Externally publishedYes


  • Chloride channel
  • Glioma

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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