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Function and dysfunction of the PI system in membrane trafficking

Authors
  • Vicinanza, Mariella1
  • D'Angelo, Giovanni1
  • Di Campli, Antonella1
  • De Matteis, Maria Antonietta1
  • 1 Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
Type
Published Article
Journal
The EMBO Journal
Publisher
EMBO
Publication Date
Sep 11, 2008
Volume
27
Issue
19
Pages
2457–2470
Identifiers
DOI: 10.1038/emboj.2008.169
PMID: 18784754
PMCID: PMC2536629
Source
PubMed Central
Keywords
License
Green

Abstract

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.

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