Ptdlns5P regulation through evolution: roles in membrane trafficking?

Phosphoinositides are lipid second messengers that are essential for many cellular processes, including signal transduction and cell compartmentalization. Among them, phosphatidlylinositol 5-phosphate (Ptdins5P) is the least characterized, although several proteins involved in its regulation are implicated in human diseases. We studied the distribution of 32 Ptdins5P-metabolizing proteins in 39 eukaryotic genomes. Phylogenetic profiles identify four groups of co-evolving proteins, confirming known protein complexes and revealing new ones. The complexes comprise a phosphatase, a kinase and a regulator; this indicates that physical interactions between the three partners are necessary for the acute spatial regulation of Ptdlns5P turnover. By examining Ptdlns5P metabolism in this new perspective, we propose a role for Ptdlns5P in membrane trafficking from late endosomal compartments to the plasma membrane.