Cdc42 GTPase dynamics control directional growth responses

Polarized cells reorient their direction of growth in response toenvironmental cues. In the fungus Candida albicans, the Rho-familysmall GTPase, Cdc42, is essential for polarized hyphal growth andCa2+ influx is required for the tropic responses of hyphae to environmental cues, but the regulatory link between these systems isunclear. In this study, the interaction between Ca2+ influx and Cdc42polarity-complex dynamics was investigated using hyphal galvano-tropic and thigmotropic responses as reporter systems. During polarity establishment in an applied electric field, cathodal emergenceof hyphae was lost when either of the two Cdc42 apical recyclingpathways was disrupted by deletion of Rdi1, a guanine nucleotidedissociation inhibitor, or Bnr1, a formin, but was completely restored by extracellular Ca2+. Loss of the Cdc42 GTPase activatingproteins, Rga2 and Bem3, also abolished cathodal polarization, butthis was not rescued by Ca2+. Expression of GTP-locked Cdc42 reversed the polarity of hypha emergence from cathodal to anodal, aneffect augmented by Ca2+. The cathodal directional cue thereforerequires Cdc42 GTP hydrolysis. Ca2+ influx amplifies Cdc42-mediateddirectional growth signals, in part by augmenting Cdc42 apical trafficking. The Ca2+-binding EF-hand motif in Cdc24, the Cdc42 activator, was essential for growth in yeast cells but not in establishedhyphae. The Cdc24 EF-hand motif is therefore essential for polarityestablishment but not for polarity maintenance.