The multiple roles of PtdIns(4)P -- not just the precursor of PtdIns(4,5)P2.
The phosphoinositides (PIs) are membrane phospholipids that actively operate at membrane-cytosol interfaces through the recruitment of a number of effector proteins. In this context, each of the seven different PI species represents a topological determinant that can establish the nature and the function of the membrane where it is located. Phosphatidylinositol 4-phosphate (PtdIns(4)P) is the most abundant of the monophosphorylated inositol phospholipids in mammalian cells, and it is produced by D-4 phosphorylation of the inositol ring of PtdIns. PtdIns(4)P can be further phosphorylated to PtdIns(4,5)P(2) by PtdIns(4)P 5-kinases and, indeed, PtdIns(4)P has for many years been considered to be just the precursor of PtdIns(4,5)P(2). Over the last decade, however, a large body of evidence has accumulated that shows that PtdIns(4)P is, in its own right, a direct regulator of important cell functions. The subcellular localisation of the PtdIns(4)P effectors initially led to the assumption that the bulk of this lipid is present in the membranes of the Golgi complex. However, the existence and physiological relevance of ;non-Golgi pools' of PtdIns(4)P have now begun to be addressed. The aim of this Commentary is to describe our present knowledge of PtdIns(4)P metabolism and the molecular machineries that are directly regulated by PtdIns(4)P within and outside of the Golgi complex.
Laboratory of Secretion Physiopathology, Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro (CH), Italy.
Giovanni
G
D'Angelo
Mariella
M
Vicinanza
Antonella
A
Di Campli
Maria Antonietta
MA
De Matteis
D019870:1-Phosphatidylinositol 4-Kinase / Q000235:genetics / Q000378:metabolism*; D051339:Actin Depolymerizing Factors / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000502:physiology*; D018129:Phosphatidylinositol Phosphates / Q000502:physiology*; D010716:Phosphatidylinositols / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000099182:Phosphoinositide 5-Phosphatases
D019870:1-Phosphatidylinositol 4-Kinase; D051339:Actin Depolymerizing Factors; D033942:Adaptor Proteins, Vesicular Transport; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D010744:Phosphoric Monoester Hydrolases; D029701:Saccharomyces cerevisiae Proteins; D000099182:Phosphoinositide 5-Phosphatases; C037178:phosphatidylinositol 4-phosphate; C053153:phosphatidylinositol-3,4-bisphosphate 4-phosphatase