Striking a balance: PIP(2) and PIP(3) signaling in neuronal health and disease

Phosphoinositides are membrane phospholipids involved in a variety of cellular processes like growth, development, metabolism, and transport. This review focuses on the maintenance of cellular homeostasis of phosphatidylinositol 4,5-bisphosphate (PIP(2)), and phosphatidylinositol 3,4,5-trisphosphate (PIP(3)). The critical balance of these PIPs is crucial for regulation of neuronal form and function. The activity of PIP(2) and PIP(3) can be regulated through kinases, phosphatases, phospholipases and cholesterol microdomains. PIP(2) and PIP(3) carry out their functions either indirectly through their effectors activating integral signaling pathways, or through direct regulation of membrane channels, transporters, and cytoskeletal proteins. Any perturbations to the balance between PIP(2) and PIP(3) signaling result in neurodevelopmental and neurodegenerative disorders. This review will discuss the upstream modulators and downstream effectors of the PIP(2) and PIP(3) signaling, in the context of neuronal health and disease.