How Neuromembrane Lipids Modulate Membrane Proteins: Insights from G-Protein-Coupled Receptors (GPCRs) and Receptor Tyrosine Kinases (RTKs).

Lipids play a diverse and critical role in cellular processes in all tissues. The unique lipid composition of nerve membranes is particularly interesting because it contains, among other things, polyunsaturated lipids, such as docosahexaenoic acid, which the body only gets through the diet. The crucial role of lipids in neurological processes, especially in receptor-mediated cell signaling, is emphasized by the fact that in many neuropathological diseases there are significant deviations in the lipid composition of nerve membranes compared to healthy individuals. The lipid composition of neuromembranes can significantly affect the function of receptors by regulating the physical properties of the membrane or by affecting specific interactions between receptors and lipids. In addition, it is worth noting that the ligand-binding pocket of many receptors is located inside the cell membrane, due to which lipids can even modulate the binding of ligands to their receptors. These mechanisms highlight the importance of lipids in the regulation of membrane receptor activation and function. In this article, we focus on two major protein families: G-protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) and discuss how lipids affect their function in neuronal membranes, elucidating the basic mechanisms underlying neuronal function and dysfunction.