Spatial organization of phosphoinositide signaling

Mammalian cells express seven distinct phosphoinositide species: PI(3)P, PI(4)P, PI(5)P, PI(3,4)P 2 , PI(3,5)P 2 , PI(4,5)P 2 , and PI(3,4,5)P 3 . With the rapid development of labeling, imaging, and manipulation tools, our understanding of the spatial distribution, functions, and regulation of these phosphoinositides has advanced significantly. Tightly regulated by lipid kinases, phosphatases, and lipid transfer proteins, each phosphoinositide exhibits a unique yet dynamic spatial distribution at both subcellular and suborganelle levels. This distinct spatial organization is critical for controlling membrane trafficking, defining organelle identity and function, mediating signal transduction, and supporting other essential cellular processes. Dysregulation of spatial phosphoinositide signaling has been linked to various human diseases. In this review, we provide a brief overview of current insights into the spatial organization of phosphoinositide signaling, highlighting its key roles in regulating membrane dynamics and signal transduction at the plasma membrane, endosomes and lysosomes, the Golgi apparatus, the ER, and the nucleus.