Phosphoinositides and Membrane Targeting in Cell Polarity

Selective enrichment of the polyphosphoinositides (PPIn), such as PtdIns(4,5)P₂ and PtdIns4P, helps to determine the identity of the plasma membrane (PM) and regulates many aspects of cell biology through a vast number of protein effectors. Polarity proteins had long been assumed to be non-PPIn-binding proteins that mainly associate with PM/cell cortex through their extensive protein-protein interaction network. However, recent studies began to reveal that several key polarity proteins electrostatically bind to PPIn through their positively charged protein domains or structures and such PPIn-binding property is essential for their direct and specific attachment to PM. Although the physical nature of the charge-based PPIn binding appears to be simple and nonspecific, it serves as an elegant mechanism that can be efficiently and specifically regulated for achieving polarized PM targeting of polarity proteins. As an unexpected consequence, subcellular localization of PPIn-binding polarity proteins are also subject to regulations by physiological conditions such as hypoxia and ischemia that acutely and reversibly depletes PPIn from PM.