Cell membrane cholesterol and lipid microdomains (Lipid rafts) (Lipid rafts)

Cell membrane cholesterol and lipid microdomains, commonly referred to as lipid rafts, are specialized, dynamic regions of the plasma membrane enriched in cholesterol, sphingolipids, and specific proteins (Pike, 2006). These microdomains function as organized platforms that compartmentalize cellular processes, particularly signal transduction, membrane trafficking, and the assembly of viral particles (Simons & Toomre, 2000). By concentrating signaling molecules such as G protein-coupled receptors and tyrosine kinases, lipid rafts facilitate efficient communication between the extracellular environment and the cell interior. In various diseases, these domains are hijacked; for instance, many viruses, including HIV-1 and SARS-CoV-2, utilize lipid rafts for entry and budding (Lu et al., 2008). In cancer, they often harbor overactive growth factor receptors that drive tumor progression and provide resistance to apoptosis. Therapeutic strategies targeting these microdomains often involve the use of cholesterol-depleting agents or alkylphospholipids to disrupt raft integrity and inhibit pathological signaling (Mollinedo et al., 2010). However, because these structures are fundamental to normal cell physiology, achieving selectivity remains a significant challenge in drug development.

Other names

Lipid raftsMembrane raftsDetergent-resistant membranes (DRMs)Cholesterol-rich microdomainsCaveolaeGlycolipid-enriched membrane microdomains (GEMs)

Drugs targeting these microdomains typically act by depleting or sequestering membrane cholesterol, which leads to the structural disintegration of the rafts and the subsequent displacement or inactivation of raft-resident signaling proteins and receptors (Simons & Toomre, 2000). Some agents, such as edelfosine, selectively accumulate in rafts to trigger pro-apoptotic signaling cascades (Mollinedo et al., 2010).