An intercellular polyamine transfer via gap junctions regulates proliferation and response to stress in epithelial cells

Mol Biol Cell. 2013 May;24(10):1529-43. doi: 10.1091/mbc.E12-10-0729. Epub 2013 Mar 20.

Abstract

In the organism, quiescent epithelial cells have the potential to resume cycling as a result of various stimuli, including wound healing or oxidative stress. Because quiescent cells have a low polyamine level, resuming their growth requires an increase of their intracellular polyamine levels via de novo polyamine synthesis or their uptake from plasma. Another alternative, explored here, is an intercellular exchange with polyamine-rich cycling cells via gap junctions. We show that polyamines promote gap junction communication between proliferating cells by promoting dynamical microtubule plus ends at the cell periphery and thus allow polyamine exchange between cells. In this way, cycling cells favor regrowth in adjacent cells deprived of polyamines. In addition, intercellular interactions mediated by polyamines can coordinate the translational response to oxidative stress through the formation of stress granules. Some putative in vivo consequences of polyamine-mediated intercellular interactions are also discussed regarding cancer invasiveness and tissue regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Animals
  • Biological Transport
  • Cell Communication
  • Cell Line
  • Cell Movement
  • Cell Proliferation*
  • Coculture Techniques
  • Cyclohexylamines / pharmacology
  • Eflornithine / pharmacology
  • Epithelial Cells / drug effects
  • Epithelial Cells / physiology*
  • Epithelial Cells / ultrastructure
  • Gap Junctions / metabolism*
  • Microtubules / metabolism
  • Ornithine Decarboxylase / metabolism
  • Ornithine Decarboxylase Inhibitors
  • Oxidative Stress*
  • Polyamines / metabolism
  • Putrescine / metabolism*
  • Rats
  • Spermine Synthase / antagonists & inhibitors
  • Stress Fibers / metabolism

Substances

  • Cyclohexylamines
  • Ornithine Decarboxylase Inhibitors
  • Polyamines
  • Spermine Synthase
  • Ornithine Decarboxylase
  • N-(3-aminopropyl)cyclohexylamine
  • Putrescine
  • Eflornithine