TRPM7 ion channels are required for sustained phosphoinositide 3-kinase signaling in lymphocytes

Cell Metab. 2008 Jul;8(1):84-93. doi: 10.1016/j.cmet.2008.06.002.

Abstract

Lymphocytes lacking the TRPM7 (transient receptor potential cation channel, subfamily M, member 7) dual function ion channel/protein kinase exhibit a unique phenotype: they are unable to proliferate in regular media, but proliferate normally in media supplemented with 10-15 mM extracellular Mg(2+). Here, we have analyzed the molecular mechanisms underlying this phenotype. We find that upon transition from proliferation-supporting Mg(2+)-supplemented media to regular media, TRPM7-deficient cells rapidly downregulate their rate of growth, resulting in a secondary arrest in proliferation. The downregulated growth rate of transitioning cells is associated with a deactivation of signaling downstream from phosphoinositide 3-kinase, and expression of constitutively active p110 phosphoinositide 3-kinase is sufficient to support growth and proliferation of TRPM7-deficient cells in regular media. Together, these observations indicate that TRPM7 channels are required for sustained phosphoinositide 3-kinase-dependent growth signaling and therefore, that TRPM7 is positioned alongside phosphoinositide 3-kinases as a central regulator of lymphocyte growth and proliferation.

Publication types

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

MeSH terms

  • Animals
  • Cell Line
  • Cell Proliferation
  • Chickens
  • Lymphocytes / cytology
  • Lymphocytes / metabolism*
  • Magnesium
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Signal Transduction*
  • TRPM Cation Channels / physiology*

Substances

  • TRPM Cation Channels
  • Phosphatidylinositol 3-Kinases
  • Magnesium