Dynamics of Phosphoinositides in Membrane Retrieval and Insertion

The phosphoinositides PtdIns(4,5)P2 and PtdIns(3,4,5)P3 are concentrated in plasma membranes of eukaryotic cells, and excluded from endosomes, whereas PtdIns(3)P is formed in these latter intracellular membranes and is apparently excluded from the plasma membrane. The logic of this asymmetric disposition is now revealed by the nature of the effector proteins that selectively bind these lipids through specific modules and by the processes that they catalyze. PtdIns(3,4,5)P3 has a role in directing exocytosis, in addition to many other signaling events, whereas PtdIns(4,5)P2 directs endocytosis through its ability to anchor several coat proteins to the plasma membrane. Remarkably, the elimination of PtdIns(4,5)P2 from forming endosomes may be required for membrane fission to occur. Thus membrane insertion and retrieval can be regulated by plasma membrane concentrations of PtdIns(3,4,5)P3 and PtdIns(4,5)P2, whereas PtdIns(3)P directs the downstream trafficking and recycling of intracellular membranes through its attraction of proteins that catalyze these processes. The phosphoinositides thereby control many cell features that depend upon protein sorting, including the composition of the plasma membrane itself, which in turn determines the cell's responses to its environment.