Membranes: a meeting point for lipids, proteins and therapies

• Introduction • Membrane lipid composition • Membrane lipid structure • Membrane lipid organization ‐ Why so many different lipids? ‐ Lipid mixing and demixing ‐ Lateral pressure ‐ Surface electrostatics • Role of lipids in cell functions • Lipid influence in transmembrane protein function ‐ Prokaryotic potassium channel (KcsA) ‐ Mechanosensitive channels ‐ Voltage‐gated potassium channel (KvAP) ‐ Nicotinic acetylcholine receptor (nAcChR) ‐ G protein‐coupled receptors ‐ Other examples • Non‐permanent proteins in membranes ‐ Proteins that interact reversibly with the bilayers ‐ Proteins that interact irreversibly with the bilayers ‐ Proteins that interact weakly with the membrane ‐ Proteins that interact strongly with the membrane ‐ G proteins and their interactions with membranes ‐ Small monomeric G proteins: the Ras and Ras‐like family ‐ Protein kinase C • Membrane microdomains and lipid mediators in the control of heat‐shock protein response ‐ Stress sensing and signalling: the membrane sensor theory ‐ Hsp signalling in cancer and diabetes ‐ The role of membrane microdomains ‐ Lipid mediators of the stress response • A subpopulation of Hsps can interact with and translocate through membranes ‐ Hsp90 in eukaryotic membranes ‐ Hsp70 in cell membranes ‐ Hsp27‐membrane interactions ‐ Secreted Hsps ‐ Representative cases where Hsps interact with membranes or release from the cells • Concluding remarks Membranes constitute a meeting point for lipids and proteins. Not only do they define the entity of cells and cytosolic organelles but they also display a wide variety of important functions previously ascribed to the activity of proteins alone. Indeed, lipids have commonly been considered a mere support for the transient or permanent association of membrane proteins, while acting as a selective cell/organelle barrier. However, mounting evidence demonstrates that lipids themselves regulate the location and activity of many membrane proteins, as well as defining membrane microdomains that serve as spatio‐temporal platforms for interacting signalling proteins. Membrane lipids are crucial in the fission and fusion of lipid bilayers and they also act as sensors to control environmental or physiological conditions. Lipids and lipid structures participate directly as messengers or regulators of signal transduction. Moreover, their alteration has been associated with the development of numerous diseases. Proteins can interact with m