Function and dysfunction of the PI system in membrane trafficking

• Published in: The EMBO journal Vol. 27; no. 19; pp. 2457 - 2470
• Main Authors: Vicinanza, Mariella, D'Angelo, Giovanni, Di Campli, Antonella, De Matteis, Maria Antonietta
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 08.10.2008; Nature Publishing Group UK; Blackwell Publishing Ltd; Nature Publishing Group
• Subjects: 1-Phosphatidylinositol 4-Kinase - genetics; 1-Phosphatidylinositol 4-Kinase - metabolism; Animals; Cell Membrane - chemistry; Cell Membrane - metabolism; Enzymes; genetic diseases; Humans; Intracellular Membranes - chemistry; Intracellular Membranes - metabolism; Kinases; Membrane Lipids - chemistry; Membrane Lipids - metabolism; membrane trafficking; Membranes; Metabolism; Molecular biology; New EMBO Member's Review; Phosphatidylinositols - metabolism; phosphoinositides; Phosphoric Monoester Hydrolases - genetics; Phosphoric Monoester Hydrolases - metabolism; Protein Transport - physiology; Signal Transduction - physiology; genetic diseases; membrane trafficking; phosphoinositides
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/emboj.2008.169

The phosphoinositides (PIs) function as efficient and finely tuned switches that control the assembly–disassembly cycles of complex molecular machineries with key roles in membrane trafficking. This important role of the PIs is mainly due to their versatile nature, which is in turn determined by their fast metabolic interconversions. PIs can be tightly regulated both spatially and temporally through the many PI kinases (PIKs) and phosphatases that are distributed throughout the different intracellular compartments. In spite of the enormous progress made in the past 20 years towards the definition of the molecular details of PI–protein interactions and of the regulatory mechanisms of the individual PIKs and phosphatases, important issues concerning the general principles of the organisation of the PI system and the coordination of the different PI‐metabolising enzymes remain to be addressed. The answers should come from applying a systems biology approach to the study of the PI system, through the integration of analyses of the protein interaction data of the PI enzymes and the PI targets with those of the ‘phenomes’ of the genetic diseases that involve these PI‐metabolising enzymes.