Here, we explore how PI (3,5)P 2 levels within cells are regulated. We find the PIKfyve complex comprises five copies of the scaffolding protein Vac14 and one copy each of the lipid kinase PIKfyve, generating PI (3,5)P 2 from PI3P and the lipid phosphatase Fig4, reversing the reaction.

2010年7月13日 · In this paper, by direct patch-clamping of the endolysosomal membrane, we report that PI (3,5)P 2, an endolysosome-specific PIP, binds and activates endolysosome-localized mucolipin transient...

Phosphatidylinositol 3,5-bisphosphate is in very low abundance and is required for retrograde membrane trafficking from lysosomal and late endosomal compartments to the Golgi and is involved in autophagy.

2023年9月4日 · Using the amoeba Dictyostelium discoideum, we identify SnxA as a highly selective PI (3,5)P2-binding protein and characterize its use as a reporter for PI (3,5)P2 in both Dictyostelium and mammalian cells.

Here, using biochemical characterization of isolated yeast vacuolar vesicles, we demonstrate that addition of exogenous short-chain PI (3,5)P2 to Vph1-containing vacuolar vesicles activates V-ATPase activity and proton pumping.

2008年9月11日 · With the PI response to cell stress, in their seminal paper identifying PtdIms 3,5‐bisphosphate (PI35P2) as a novel endogenous PI species, Dove et al reported that PI35P2 levels increase by up to 30‐fold in yeast cells subjected to hyperosmotic stress.

TORC1, a conserved protein kinase, regulates cell growth in response to nutrients. Localization of mammalian TORC1 to lysosomes is essential for TORC1 activation. Phosphatidylinositol 3,5-bisphosphate (PI(3,5)P(2)), an endosomal signaling lipid, is implicated in insulin-dependent stimulation of TORC …

2023年8月14日 · Since its discovery in 1997 (2), PI (3,5)P 2 has become one of the most enigmatic lipid pathways in animal cells but has also shown great promise for clinical exploitation. It is known to regulate the endocytic pathway, principally at the …

Here, we identify the branched actin regulator cortactin as a direct binding partner of phosphatidylinositol 3,5-bisphosphate (PI (3,5)P 2) and demonstrate that their interaction promotes turnover of late endosomal actin. In vitro biochemical studies indicated that cortactin binds PI (3,5)P 2 via its actin filament-binding region.

Although the cellular levels of phosphatidylinositol 5-phosphate (PI5P) and phosphatidylinositol 3,5-bisphosphate (PI (3,5)P 2) are extremely low relative to some other PIs, emerging evidence demonstrates that both lipids are crucial for the endocytic pathway, intracellular signaling, and adaptation to stress.