A novel phosphatidylinositol(3,4,5)P3 pathway in fission yeast

Abstract

The mammalian tumor suppressor, phosphatase and tensin homologue deleted on chromosome 10 (PTEN), inhibits cell growth and survival by dephosphorylating phosphatidylinositol-(3,4,5)-trisphosphate (PI[3,4,5]P3). We have found a homologue of PTEN in the fission yeast, Schizosaccharomyces pombe (ptn1). This was an unexpected finding because yeast (S. pombe and Saccharomyces cerevisiae) lack the class I phosphoinositide 3-kinases that generate PI(3,4,5)P3 in higher eukaryotes. Indeed, PI(3,4,5)P3 has not been detected in yeast. Surprisingly, upon deletion of ptn1 in S. pombe, PI(3,4,5)P3 became detectable at levels comparable to those in mammalian cells, indicating that a pathway exists for synthesis of this lipid and that the S. pombe ptn1, like mammalian PTEN, suppresses PI(3,4,5)P3 levels. By examining various mutants, we show that synthesis of PI(3,4,5)P3 in S. pombe requires the class III phosphoinositide 3-kinase, vps34p, and the phosphatidylinositol-4-phosphate 5-kinase, its3p, but does not require the phosphatidylinositol-3-phosphate 5-kinase, fab1p. These studies suggest that a pathway for PI(3,4,5)P3 synthesis downstream of a class III phosphoinositide 3-kinase evolved before the appearance of class I phosphoinositide 3-kinases.

PXA Domain-Containing Protein Pxa1 Is Required for Normal Vacuole Function and Morphology inSchizosaccharomyces pombe

“…These phenotypes are similar to those observed in class E Vps mutants such sst4/vps27Á and sst6Á. 39) In addition, Pxa1p is required for recycling of Vps10p from the endosome to the Golgi compartment (Fig. 3C).…”

Characterization of Mid1 domains for targeting and scaffolding in fission yeast cytokinesis

“…3D) and tested its binding with lipids spotted on a nitrocellulose membrane. Compared with the positive 6His-Ksg1(PH) (Mitra et al, 2004) and negative 6His-mEGFP controls, we found that 6His-Mid1(PH) interacts with several lipids (Fig. 3E).…”

Two distinct functions for PI3-kinases in macropinocytosis

“…The source of the remaining PtdIns(3,4,5)P 3 is currently unknown, but PikH, an unusual PI3-kinase with a PH-domain, is unlikely to be responsible, as a sextuple mutant with this gene also knockedout, has a similar residual level of PtdIns(3,4,5)P 3 (unpublished observation). We hypothesize that, as in fission yeast, a metabolic pathway starting from PtdIns(3)P, generated by PikE, the Dictyostelium homologue of Vps34, may be responsible (Mitra et al, 2004).…”