A brief history of phosphatidylinositol transfer proteins: from the backwaters of cell biology to prime time in lipid signaling

Abstract

How lipids are sorted between intracellular compartments and what mechanisms support inter-organellar lipid transport define questions that have enjoyed long-standing interest in the cell biology community. Despite tantalizing evidence to the effect that lipids can move between organelles independently of standard modes of vesicular membrane trafficking through the secretory pathway, biochemical dissection of these non-vesicular pathways was initially fraught with experimental challenges. Many of the obstacles have now been overcome and, following initial breakthroughs, the last two decades have witnessed a renaissance in the field of lipid trafficking. Indeed, lipid trafficking and mobilization are now significant components of any discussion regarding secretory vesicle trafficking, organelle biogenesis, agonist-stimulated lipid signaling, and inter-compartmental communication pathways that involve every organelle in the eukaryotic cell. In accord with the theme of this special issue, we focus on the topic of soluble lipid transfer proteins that interface with the metabolism of phosphatidylinositol (PtdIns) and its phosphorylated derivatives – the phosphoinositides. Although phosphoinositides are quantitatively minor lipids in cells, these molecules represent the chemical codes for a major pathway of intracellular signaling in all eukaryotic cells. It is now clear that soluble PtdIns transfer proteins (PITPs) are physiologically critical regulators of specific pathways of phosphoinositide – particularly PtdIns-4-phosphate – signaling. The ‘where’ PITPs determine the biological outcomes of phosphoinositide signaling, and the ‘how’ by which PITPs do so, represent increasingly active areas of research in contemporary cell biology. It is these issues we explore from a historical perspective with a focus on the Sec14-like PITPs.