Protein targeting to endosomes and phagosomes via FYVE and PX domains

Phosphatidylinositol 3-phosphate (PI3P) is generated on early endosomal and phagosomal membranes by PI 3-kinases. This lipid serves important regulatory functions in phagocytosis, endocytic traffic, receptor signalling and microbial killing through the recruitment and activation of a number of effector proteins. Almost all of these effectors contain FYVE or PX domains, functional protein modules which are conserved from yeast to mammals. Structural information is available regarding the binding of FYVE and PX domains to PI3P. The two domains are highly different, but they have in common that clusters of basic residues mediate ligand binding through interactions with the phosphate groups of PI3P. Most proteins that contain FYVE or PX domains serve as regulators of endocytic membrane trafficking, whereas others function as regulators of phagosome maturation, signal transduction, microbial killing and other cellular activities of relevance for the immune system.