Model for the PI(4,5)P2-septin cell wall regulatory network. Exposure of C. albicans to caspofungin inhibits β-1,3-d-glucan synthesis and creates cell wall stress (box 1). Upon sensing this stress, cells rapidly redistribute PI(4,5)P2 and septins (box 3). PI(4,5)P2 accumulation activates the PKC-MAPK cell wall integrity pathway, and PI(4,5)P2 and septins direct the deposit of chitin and other cell wall components at sites of colocalization (box 4). The redistribution of PI(4,5)P2 and septins in response to caspofungin is similar to that observed in gin4, irs4, and inp51 mutants, which are hypersusceptible to caspofungin and exhibit highly similar cell wall damage response gene expression profiles. Therefore, the data suggest that (i) Gin4 and the Irs4/Inp51 5′-phosphatase complex function upstream of PI(4,5)P2 and septins in a pathway that relays the cell wall stress signal (box 2), and (ii) an intact Gin4-Irs4/Inp51-PI(4,5)P2-septin pathway is required for the maintenance of cell wall integrity in the face of ongoing caspofungin exposure (box 5). Cell wall regulation (CWR) through the pathway is part of the natural response to caspofungin and, as our earlier mouse data indicated (), necessary for the progression of invasive candidiasis after the initial stages of tissue colonization (box 6). White and blue boxes represent components of this model that have been established or suggested by our data, respectively.