Phosphoinositide and Lipid Dynamics
Phosphoinositides (PIPs), the phosphorylated metabolites of phosphatidylinositol, are membrane phospholipids that play critical roles in cell regulation. Among membrane lipids, phosphoinositides are powerful regulatory molecules because their differentially phosphorylated inositol group can interact with variable specificity with cytosolic protein modules or with cytoplasmic regions of transmembrane proteins, thus controlling virtually every aspect of neuronal function including membrane-cytoskeleton interactions, membrane traffic, nuclear events, neurotransmitter release and the transduction of neurotransmitter signals. Importantly, the phosphoinositide signaling system is closely interrelated with intracellular signaling pathways involved in the actions of drugs of abuse.
Advanced technologies that are available include:
- Liposome-based protein-lipid binding
- Lipid transfer or exchange between liposomes
- Microscopy assays, including Correlative Light and Electron Microscopy (CLEM) and Focused Ion Beam-Scanning Electron Microscopy-CLEM (FIB-SEM-CLEM) for the detection of specific lipids using fluorescent reporters
- Chemogenetic and optogenetic approaches to acutely manipulate the activity of specific phosphoinositide metabolizing enzymes and lipid transport proteins in living cells