Phosphatidylinositol transfer proteins and instructive regulation of lipid kinase biology

• Published in: Biochimica et biophysica acta Vol. 1851; no. 6; pp. 724 - 735
• Main Authors: Grabon, Aby, Khan, Danish, Bankaitis, Vytas A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2015
• Subjects: Biological Transport; CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase - genetics; CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase - metabolism; enzymes; eukaryotic cells; Gene Expression Regulation; Humans; inositol phosphates; Lipid Metabolism; lipids; Models, Molecular; Phosphatidylinositol transfer proteins; Phosphatidylinositols - metabolism; Phospholipid Transfer Proteins - genetics; Phospholipid Transfer Proteins - metabolism; Phosphotransferases (Alcohol Group Acceptor) - genetics; Phosphotransferases (Alcohol Group Acceptor) - metabolism; physiology; proteins; Regulation of lipid kinases; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Signal Transduction; Signaling diversity; Type C Phospholipases - genetics; Type C Phospholipases - metabolism; Signaling diversity; Phosphatidylinositol transfer proteins; Regulation of lipid kinases
• ISSN: 1388-1981; 0006-3002; 1879-2618; 1878-2434
• DOI: 10.1016/j.bbalip.2014.12.011

Phosphatidylinositol is a metabolic precursor of phosphoinositides and soluble inositol phosphates. Both sets of molecules represent versatile intracellular chemical signals in eukaryotes. While much effort has been invested in understanding the enzymes that produce and consume these molecules, central aspects for how phosphoinositide production is controlled and functionally partitioned remain unresolved and largely unappreciated. It is in this regard that phosphatidylinositol (PtdIns) transfer proteins (PITPs) are emerging as central regulators of the functional channeling of phosphoinositide pools produced on demand for specific signaling purposes. The physiological significance of these proteins is amply demonstrated by the consequences that accompany deficits in individual PITPs. Although the biological problem is fascinating, and of direct relevance to disease, PITPs remain largely uncharacterized. Herein, we discuss our perspectives regarding what is known about how PITPs work as molecules, and highlight progress in our understanding of how PITPs are integrated into cellular physiology. This article is part of a Special Issue entitled Phosphoinositides. •Historical views of PITPs as lipid transfer proteins are reassessed.•PITPs channel lipid kinase activities to specific biological outcomes.•Mechanisms of functional channeling rest on PITP ligand specificities.•PITP lipid exchange cycle is an engine for potentiating lipid kinase catalytic efficiency.