Function and dysfunction of the PI system in membrane trafficking

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 the...

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Bibliographic Details
Published in:The EMBO journal 2008-10, Vol.27 (19), p.2457-2470
Main Authors: Vicinanza, Mariella, D'Angelo, Giovanni, Di Campli, Antonella, De Matteis, Maria Antonietta
Format: Article
Language:English
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
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Phosphatidylinositols - metabolism
phosphoinositides
Phosphoric Monoester Hydrolases - genetics
Phosphoric Monoester Hydrolases - metabolism
Protein Transport - physiology
Signal Transduction - physiology
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Summary: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.
ISSN:0261-4189
1460-2075
DOI:10.1038/emboj.2008.169