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Function and dysfunction of the PI system in membrane trafficking.

Vicinanza M, D'Angelo G, Di Campli A, De Matteis MA - EMBO J. (2008)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy.

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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Subcellular distribution of the PIs and PI-metabolising enzymes. The localisation of the different PIKs (blue) and PI phosphatases (green), as well as the predominant PI species (as visualised by PI-binding protein domains) in the different cell compartments. It is noted that many of the PI-metabolising enzymes are present in more than one cellular compartment, and their overall distributions do not completely fit with the PI map, as indicated using the PI-binding protein probes (see text for details). The PIKs and PI phosphatases are indicated according to the nomenclature given in Figure 1. PM, plasma membrane; EE, early endosome; SE: sorting endosomes; RE, recycling endosome; LY, lysosome; MVB/LE, multivesicular body/late endosome; PAS, pre-autophagosomal structure; PH, phagosome; TGN, trans-Golgi network; GC, Golgi complex; ER: endoplasmic reticulum; N, nucleus.
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f2: Subcellular distribution of the PIs and PI-metabolising enzymes. The localisation of the different PIKs (blue) and PI phosphatases (green), as well as the predominant PI species (as visualised by PI-binding protein domains) in the different cell compartments. It is noted that many of the PI-metabolising enzymes are present in more than one cellular compartment, and their overall distributions do not completely fit with the PI map, as indicated using the PI-binding protein probes (see text for details). The PIKs and PI phosphatases are indicated according to the nomenclature given in Figure 1. PM, plasma membrane; EE, early endosome; SE: sorting endosomes; RE, recycling endosome; LY, lysosome; MVB/LE, multivesicular body/late endosome; PAS, pre-autophagosomal structure; PH, phagosome; TGN, trans-Golgi network; GC, Golgi complex; ER: endoplasmic reticulum; N, nucleus.

Mentions: The phosphoinositides (PIs) derive from reversible phosphorylation in three of the five hydroxyl groups of the inositol headgroup of the ‘parent' PI, phosphatidylinositol (PtdIns). This process operates through the large repertoire of PI kinases (PIKs) and PI phosphatases that are present in practically all cell compartments (Figures 1 and 2). The combined activities of the various isoforms of these PIKs and PI phosphatases provide a dynamic equilibrium between the seven distinct, but interconvertible, PI species (Figure 1). It is now clear that all of these different PIs are ‘active' in their own right, rather than many just serving as intermediates in the synthesis of the higher phosphorylated species.


Function and dysfunction of the PI system in membrane trafficking.

Vicinanza M, D'Angelo G, Di Campli A, De Matteis MA - EMBO J. (2008)

Subcellular distribution of the PIs and PI-metabolising enzymes. The localisation of the different PIKs (blue) and PI phosphatases (green), as well as the predominant PI species (as visualised by PI-binding protein domains) in the different cell compartments. It is noted that many of the PI-metabolising enzymes are present in more than one cellular compartment, and their overall distributions do not completely fit with the PI map, as indicated using the PI-binding protein probes (see text for details). The PIKs and PI phosphatases are indicated according to the nomenclature given in Figure 1. PM, plasma membrane; EE, early endosome; SE: sorting endosomes; RE, recycling endosome; LY, lysosome; MVB/LE, multivesicular body/late endosome; PAS, pre-autophagosomal structure; PH, phagosome; TGN, trans-Golgi network; GC, Golgi complex; ER: endoplasmic reticulum; N, nucleus.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2536629&req=5

f2: Subcellular distribution of the PIs and PI-metabolising enzymes. The localisation of the different PIKs (blue) and PI phosphatases (green), as well as the predominant PI species (as visualised by PI-binding protein domains) in the different cell compartments. It is noted that many of the PI-metabolising enzymes are present in more than one cellular compartment, and their overall distributions do not completely fit with the PI map, as indicated using the PI-binding protein probes (see text for details). The PIKs and PI phosphatases are indicated according to the nomenclature given in Figure 1. PM, plasma membrane; EE, early endosome; SE: sorting endosomes; RE, recycling endosome; LY, lysosome; MVB/LE, multivesicular body/late endosome; PAS, pre-autophagosomal structure; PH, phagosome; TGN, trans-Golgi network; GC, Golgi complex; ER: endoplasmic reticulum; N, nucleus.
Mentions: The phosphoinositides (PIs) derive from reversible phosphorylation in three of the five hydroxyl groups of the inositol headgroup of the ‘parent' PI, phosphatidylinositol (PtdIns). This process operates through the large repertoire of PI kinases (PIKs) and PI phosphatases that are present in practically all cell compartments (Figures 1 and 2). The combined activities of the various isoforms of these PIKs and PI phosphatases provide a dynamic equilibrium between the seven distinct, but interconvertible, PI species (Figure 1). It is now clear that all of these different PIs are ‘active' in their own right, rather than many just serving as intermediates in the synthesis of the higher phosphorylated species.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy.

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.

Show MeSH
Related in: MedlinePlus