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Membranes define the boundaries of cells and their major organelles, enabling cellular compartmentalization that is essential for cell function. Membranes are also signalling platforms that mediate communication with the extracellular environment and between organelles. This article series brings together Reviews that focus on key advances in understanding membrane biology as well as the regulation and functions of their lipid components, including their roles as bioactive molecules and their interplay with metabolism.
Eukaryotic membrane fusion is hindered by energy barriers and often requires soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) to facilitate formation of a fusion pore. Recent studies describe SNARE activity along the fusion pathway and shed light on the regulation of SNARE complex assembly.
Despite the crucial roles of Hedgehog signalling in development and tissue regeneration, aspects of the Hedgehog signalling mechanism have been uncovered only recently. These studies reveal a central role for lipids in the Hedgehog signal activity, and provide new insights into the therapeutic potential of modulating Hedgehog signalling in tissue regeneration.
Transmembrane proteins associate with specific subsets of lipids, which create nano-environments with unique properties. Better understanding of how these nano-environments regulate protein dynamics and function will afford means to control activities of transmembrane proteins, many of which serve essential signalling and transport roles.
The generation of membrane curvature is essential for the formation of membrane tubules, sheets and vesicles, and hence, underlies membrane trafficking events. Various protein-based mechanisms function in membrane bending, and these appear to be organized in time and space by protein coats, including clathrin, caveolar coat complex, and COPI and COPII coats.
Phosphoinositides are signalling, membrane lipids derived from phosphatidylinositol, whose intracellular distribution and interconversion via phosphoinositide kinases and phosphatases is tightly coupled to membrane dynamics. Accordingly, phosphoinositides are now recognized as key regulators of endocytic and exocytic traffic, the autolysosomal system, and membrane contact site organization and function.
Integral membrane proteins make up around one quarter of the human proteome and are highly diverse in topology, biophysical features, structure and function. Their biogenesis involves multiple pathways for membrane targeting, insertion into the lipid bilayer, folding and assembly with other subunits. Recent biochemical and structural analyses have provided new insights into these mechanisms.
During cell division, the distribution of membrane-bound organelles needs to be tightly regulated to ensure the proper composition and function of daughter cells. Recent studies have shed light on the range of complex and dynamic mechanisms needed to mediate organelle inheritance and membrane remodelling during cell division.
Cholesterol is an important structural component of all animal cell membranes that functions in various processes, including membrane dynamics and cell signalling, and is also a precursor of other molecules. Deregulation of cholesterol metabolism — biosynthesis, dietary absorption and cellular uptake, storage and efflux — is linked to many diseases, including cardiovascular and genetic diseases, and cancer. A better understanding of cholesterol metabolism offers the possibility to control systemic cholesterol levels to improve human health.
Although organelles compartmentalize eukaryotic cells, they can communicate and integrate their activities by connecting at membrane contact sites (MCSs). The roles of MCSs in biology are becoming increasingly clear, with MCSs now known to function in intracellular signalling, lipid metabolism, membrane dynamics, organelle biogenesis and the cellular stress response.
Endosomal sorting complexes required for transport (ESCRTs) are key membrane remodellers, which drive the budding, scission and sealing of various cellular membranes. Accordingly, ongoing research focuses on how ESCRTs mediate a wide-range of cellular processes, including cytokinesis, endosome maturation, autophagy, membrane repair and viral replication.
Phosphoinositide 3-kinases (PI3Ks) are lipid kinases that generate 3-phosphoinositides, which govern cellular signal transduction and membrane trafficking. The PI3K family comprises three classes of enzymes, which include several isoforms and complexes; the myriad of cellular functions and means of regulation of these enzymes are now coming into focus.
Lipid droplets are storage organelles that are important for the regulation of lipid and energy homeostasis, and that serve as buffers against lipotoxicity. Recent studies on the biology of lipid droplets have led to new discoveries about their biogenesis and the complexity of their interactions with other organelles at membrane contact sites.
The distribution of lipids largely depends on their non-vesicular transport by lipid transfer proteins (LTPs). Recent progress in understanding the mechanisms of LTPs, including the appreciation of their widespread activity at membrane contact sites, has provided novel insights into the regulation of lipid trafficking and how it impacts pathophysiology.
Clathrin-mediated endocytosis is the main mechanism for internalization of cell-surface molecules and surface-bound cargoes. Although the machineries that drive the formation of endocytic vesicle are intricate, an understanding of endocytosis is being unravelled at the molecular level.
Membrane lipids exhibit a remarkable diversity — they vary in structure and chemical properties, and their distribution between different membranes and their subcompartments is highly heterogeneous. Recent progress in studies of membrane lipids has broadened our understanding of how this diversity affects membrane properties and membrane-associated processes.