Cdc42 GTPase dynamics control directional growth responses

Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):811-6. doi: 10.1073/pnas.1307264111. Epub 2014 Jan 2.


Polarized cells reorient their direction of growth in response to environmental cues. In the fungus Candida albicans, the Rho-family small GTPase, Cdc42, is essential for polarized hyphal growth and Ca(2+) influx is required for the tropic responses of hyphae to environmental cues, but the regulatory link between these systems is unclear. In this study, the interaction between Ca(2+) influx and Cdc42 polarity-complex dynamics was investigated using hyphal galvanotropic and thigmotropic responses as reporter systems. During polarity establishment in an applied electric field, cathodal emergence of hyphae was lost when either of the two Cdc42 apical recycling pathways was disrupted by deletion of Rdi1, a guanine nucleotide dissociation inhibitor, or Bnr1, a formin, but was completely restored by extracellular Ca(2+). Loss of the Cdc42 GTPase activating proteins, Rga2 and Bem3, also abolished cathodal polarization, but this was not rescued by Ca(2+). Expression of GTP-locked Cdc42 reversed the polarity of hypha emergence from cathodal to anodal, an effect augmented by Ca(2+). The cathodal directional cue therefore requires Cdc42 GTP hydrolysis. Ca(2+) influx amplifies Cdc42-mediated directional growth signals, in part by augmenting Cdc42 apical trafficking. The Ca(2+)-binding EF-hand motif in Cdc24, the Cdc42 activator, was essential for growth in yeast cells but not in established hyphae. The Cdc24 EF-hand motif is therefore essential for polarity establishment but not for polarity maintenance.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Calcium / metabolism*
  • Candida albicans / physiology*
  • Candida albicans / ultrastructure
  • Cell Enlargement*
  • Cell Membrane / metabolism*
  • Cell Polarity / physiology*
  • Hyphae / growth & development
  • Hyphae / metabolism
  • Microscopy, Electron, Transmission
  • Microscopy, Fluorescence
  • Models, Biological*
  • cdc42 GTP-Binding Protein / metabolism*


  • cdc42 GTP-Binding Protein
  • Calcium