Messengers for morphogenesis: inositol polyphosphate signaling and yeast pseudohyphal growth

Abstract

In response to various environmental stimuli and stressors, the budding yeast Saccharomyces cerevisiae can initiate a striking morphological transition from its classic growth mode as isolated single cells to a filamentous form in which elongated cells remain connected post-cytokinesis in multi-cellular pseudohyphae. The formation of pseudohyphal filaments is regulated through an expansive signaling network, encompassing well studied and highly conserved pathways enabling changes in cell polarity, budding, cytoskeletal organization, and cell adhesion; however, changes in metabolite levels underlying the pseudohyphal growth transition are less well understood. We have recently identified a function for second messenger inositol polyphosphates (InsPs) in regulating pseudohyphal growth. InsPs are formed through the cleavage of membrane-bound phosphatidylinositol 4,5-bisphosphate (PIP₂), and these soluble compounds are now being appreciated as important regulators of diverse processes, from phosphate homeostasis to cell migration. We find that kinases in the InsP pathway are required for wild-type pseudohyphal growth, and that InsP species exhibit characteristic profiles under conditions promoting filamentation. Ratios of the doubly phosphorylated InsP₇ isoforms 5PP-InsP₅ to 1PP-InsP₅ are elevated in mutants exhibiting exaggerated pseudohyphal growth. Interestingly, S. cerevisiae mutants deleted of the mitogen-activated protein kinases (MAPKs) Kss1p or Fus3p or the AMP-activated kinase (AMPK) family member Snf1p display mutant InsP profiles, suggesting that these signaling pathways may contribute to the regulatory mechanism controlling InsP levels. Consequently, analyses of yeast pseudohyphal growth may be informative in identifying mechanisms regulating InsPs, while indicating a new function for these conserved second messengers in modulating cell stress responses and morphogenesis.

Keywords: AMPK; Inositol polyphosphate; Inositol pyrophosphate; MAPK; Pseudohyphal growth; Saccharomyces cerevisiae; Yeast.