Novel Insights into the Modulation of Protein Function by Lipids and Membrane Organization

A continuously growing amount of evidence underlines the active contribution of lipids and membrane organization to the regulation of the structure and function of transmembrane proteins. In general, lipids of the cell membrane can affect proteins through a mixture of direct and indirect mechanisms. While the former comprise ligand-like binding of lipids at specific binding sites on proteins, the latter are mediated through alterations in membrane biophysical properties (fluidity, hydration, lipid order, thickness, lateral pressure and dipole potential). Furthermore, lateral segregation tendency of biological membranes into dynamic nano- and micro-domains such as cholesterol-enriched lipid rafts and ceramide platforms), and its changes in response to altered lipid composition adds a further level of complexity to the active modulatory roles of membranes in the functional regulation of proteins. By exerting permissive and cooperative actions on conformational changes associated with the activation of transmembrane proteins, such direct and indirect protein-lipid interactions can modify a large variety of cellular functions such as signaling pathways, apoptosis, cell adhesion and migration, synaptic transmission, cytoskeletal organization, protein sorting, pathogen entry, formation of amyloid plaques or extracellular vesicles, stress and immunological responses. Given that alterations in the membrane lipid composition are pathogenically relevant intrinsic characteristics of numerous human pathological conditions including metabolic (hypercholesterolemia, type 2 diabetes), neurodegenerative (Alzheimer and Parkinson disease), lysosomal storage (Niemann-Pick and Gaucher disease) disorders and tumors, elucidation of lipid- and membrane organization-related changes in protein function might reveal unexplored molecular targets that can be utilized in the therapy of these conditions.

Through collecting original research articles and reviews, this Research Topic intends to bring together a community of membrane biophysicists, cell biologists, biochemists, computational analysts, immunologists, pharmacologists and even clinical scientists to stimulate discussion and sharing of novel results, innovative tools, emerging approaches and ideas about the intrinsic connection between functional modulation of proteins and lipids and organization of cellular membranes. We invite submissions that contribute to the improvement of our collective understanding of the relevance of lipid- and membrane organization-induced alterations and their potential therapeutic targeting in human diseases.