Phosphoinositide-binding domains: Functional units for temporal and spatial regulation of intracellular signalling.

Inositol phospholipid (phosphoinositide) is a versatile lipid characterized by its isomer-specific localization, as well as its molecular diversity attributable to phosphorylation events. Phosphoinositides act as signal mediators in a spatially and temporally controlled manner. Information about the timing and location of their production is received by phosphoinositide-binding proteins and transmitted to multiple lines of intracellular events such as signal transduction, cytoskeletal rearrangement, and membrane trafficking. Among those proteins, a significant portion possess globular structural units, called domains, which are specialized for phosphoinositide binding. The pleckstrin homology (PH) domain was the first phosphoinositide-binding domain identified. It contains the largest number of members and is associated with the formation of signalling complexes on the plasma membrane. Recent studies identified other novel phosphoinositide-binding domains (Fab1p, YOTB, Vps27p, EEA1 (FYVE), Phox homology (PX), and epsin N-terminal homology (ENTH)), thus extending our knowledge of how the functional versatility of phosphoinositides is achieved.