GSK-3β is essential for physiological electric field-directed Golgi polarization and optimal electrotaxis

Cell Mol Life Sci. 2011 Sep;68(18):3081-93. doi: 10.1007/s00018-010-0608-z. Epub 2011 Jan 5.

Abstract

Endogenous electrical fields (EFs) at corneal and skin wounds send a powerful signal that directs cell migration during wound healing. This signal therefore may serve as a fundamental regulator directing cell polarization and migration. Very little is known of the intracellular and molecular mechanisms that mediate EF-induced cell polarization and migration. Here, we report that Chinese hamster ovary (CHO) cells show robust directional polarization and migration in a physiological EF (0.3-1 V/cm) in both dissociated cell culture and monolayer culture. An EF of 0.6 V/cm completely abolished cell migration into wounds in monolayer culture. An EF of higher strength (≥1 V/cm) is an overriding guidance cue for cell migration. Application of EF induced quick phosphorylation of glycogen synthase kinase 3β (GSK-3β) which reached a peak as early as 3 min in an EF. Inhibition of protein kinase C (PKC) significantly reduced EF-induced directedness of cell migration initially (in 1-2 h). Inhibition of GSK-3β completely abolished EF-induced GA polarization and significantly inhibited the directional cell migration, but at a later time (2-3 h in an EF). Those results suggest that GSK-3β is essential for physiological EF-induced Golgi apparatus (GA) polarization and optimal electrotactic cell migration.

Publication types

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

MeSH terms

  • Animals
  • Blotting, Western
  • CHO Cells
  • Cell Movement / physiology*
  • Cell Polarity / physiology
  • Cricetinae
  • Cricetulus
  • Electromagnetic Fields*
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • Golgi Apparatus / metabolism*
  • Phosphorylation
  • Protein Kinase C / antagonists & inhibitors
  • Time-Lapse Imaging
  • Wound Healing / physiology*

Substances

  • Glycogen Synthase Kinase 3 beta
  • Protein Kinase C
  • Glycogen Synthase Kinase 3