Beyond symmetry-breaking: competition and negative feedback in GTPase regulation

Trends Cell Biol. 2013 Oct;23(10):476-83. doi: 10.1016/j.tcb.2013.05.003. Epub 2013 May 31.


Cortical domains are often specified by the local accumulation of active GTPases. Such domains can arise through spontaneous symmetry-breaking, suggesting that GTPase accumulation occurs via positive feedback. Here, we focus on recent advances in fungal and plant cell models - where new work suggests that polarity-controlling GTPases develop only one 'front' because GTPase clusters engage in a winner-takes-all competition. However, in some circumstances two or more GTPase domains can coexist, and the basis for the switch from competition to coexistence remains an open question. Polarity GTPases can undergo oscillatory clustering and dispersal, suggesting that these systems contain negative feedback. Negative feedback may prevent polarity clusters from spreading too far, regulate the balance between competition and coexistence, and provide directional flexibility for cells tracking gradients.

Keywords: Cdc42; GAP; GEF; Rac; Rop.

Publication types

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

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Cell Polarity / genetics*
  • Cell Polarity / physiology
  • Feedback, Physiological
  • GTP Phosphohydrolases / genetics*
  • GTP Phosphohydrolases / metabolism
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism
  • Plant Cells / metabolism*
  • Plant Cells / physiology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • cdc42 GTP-Binding Protein / genetics
  • cdc42 GTP-Binding Protein / metabolism


  • Actins
  • GTPase-Activating Proteins
  • Guanine Nucleotide Exchange Factors
  • GTP Phosphohydrolases
  • cdc42 GTP-Binding Protein