Recent Technological Advancement in Chemical Switching of Lipid Signaling Pathways

We will recapitulate experimental techniques to rapidly and chemically perturb membrane lipids with a specific focus on phosphoinositide (PI) species. While PIs are long known as a component of the cellular membranes, the emerging evidence indicated that PIs do not represent a mere structural support, but can serve as a second messenger and actively regulate the intracellular information transfer. For example, a phosphoinositide 4,5‐bisphosphate (PIP 2 ) constitutes a small fraction of the total lipids at the plasma membrane. However, the lipid triggers diverse cellular functions as membrane trafficking, ion channel activation, cytokinesis, phagocytosis, and cell migration. Consistent with this pleiotropic role, a series of lipid kinases and phosphatases dynamically control PIs with high spatio‐temporal precision in response to various stimuli. Mutations in genes encoding these enzymes result in various human diseases, including renal, neuromuscular, and developmental disorders, many types of cancers, and diabetes. In laboratory experiments, unfortunately, these mutations often result in genetic compensations, and/or co‐lateral effects on neighbor PIs, complicating our data interpretation. Elucidating a role of PIs in native environment thus requires new generation of techniques that can rapidly and inducibly manipulate PIs in living cells. This workshop will focus the technological advancement in chemical molecular tools that enable such highly controlled manipulation of PIs.