This year celebrates the 50th anniversary of the Singer-Nicolson fluid mosaic model for biological membranes. The next level of sophistication we have achieved for understanding plasma membrane (PM) structures, dynamics, and functions during these 50 years includes the PM interactions with cortical actin filaments and the partial demixing of membrane constituent molecules in the PM, particularly raft domains. Here, first, we summarize our current knowledge of these two structures and emphasize that they are interrelated. Second, we review the structure, molecular dynamics, and function of raft domains, with main focuses on raftophilic glycosylphosphatidylinositol-anchored proteins (GPI-APs) and their signal transduction mechanisms. We pay special attention to the results obtained by single-molecule imaging techniques and other advanced microscopy methods. We also clarify the limitations of present optical microscopy methods for visualizing raft domains, but emphasize that single-molecule imaging techniques can "detect" raft domains associated with molecules of interest in the PM.
Keywords: Cholesterol; GPI-anchored proteins; Lipid rafts; Single-molecule imaging; Sphingolipids; Super-resolution microscopy.
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