Phosphoinositide-bis-phosphate is required for Saccharomyces cerevisiae invasive growth

Abstract

Phosphoinositide phosphates are important regulators of processes such as the cytoskeleton organization, membrane traffic and gene transcription, which are all critical for polarized cell growth. In particular PI(4,5)P2 plays essential roles in polarized growth as well as in cellular responses to stress. In the yeast Saccharomyces cerevisiae a sole PI(4)P-5-kinase, Mss4p is essential for generating plasma membrane PI(4,5)P2. Here we show that Mss4p is required for yeast invasive growth in low nutrient conditions. Specific mss4 mutants were isolated which are defective in cell elongation, induction of the Flo11p flocculin, adhesion and cell wall integrity. We show that mss4-f12 cells have reduced plasma membrane PI(4,5)P2 levels as well as a defect in the polarized distribution of this phospholipid, yet Mss4-f12p is catalytically active in vitro. In addition, the Mss4-f12 protein was defective in localizing to the plasma membrane. Furthermore, addition of cAMP, but not an activated MAPKKK allele, partially restored the invasive growth defect of mss4-f12 cells. Together our results indicate that plasma membrane PI(4,5)P2 is critical for yeast invasive growth and suggest that this phospholipid functions upstream of the cAMP-dependent protein kinase A signaling pathway.