Phosphatidylinositol 3,5-bisphosphate and Fab1p/PlKfyve underPPIn endo-lysosome function

PtdIns(3,5)P-2 is one of the seven regulatory PPIn (polyphosphoinositides) that are ubiquitous in eukaryotes. It controls membrane trafficking at multiple points in the endosomal/lysosomal system and consequently regulates the size, shape and acidity of at least one endo-lysosomal compartment. PtdIns(3,5)P-2 appears to exert this control via multiple effector proteins, with each effector specific for it subset of the various PtdIns(3,5)P-2-dependent processes. Some putative PtdIns(3,5)P-2 effectors have been identified, including Atg18p-related PROPPIN [beta-propeller(s) that bind PPIn] proteins and the epsin-like proteins Ent3p and Ent5p, whereas others remain to he defined. One of the principal functions of PtdIns(3,5)P-2 is to regulate the fission/fragmentation of endo-lysosomal sub-compartments. PtdIns(3,5)P-2 is required for vesicle formation during protein trafficking between endolysosomes and also for fragmentation of endo-lysosomes into smaller compartments. In yeast, hyperosmotic stress accelerates the latter process. In the present review we highlight and discuss recent Studies that reveal the role of the HOPS-CORVET complex and the vacuolar H+-ATPase in the process of endo-lysosome fission, and speculate oil connections between these machineries and the Fab1p pathway. We also discuss new evidence linking PtdIns(3,5)P-2 and PtdIns5P to the regulation of exocytosis.