Cell membrane cholesterol and sphingolipids

Cell membrane cholesterol and sphingolipids are essential structural components that organize into specialized, highly ordered microdomains known as lipid rafts. These rafts serve as dynamic platforms for signal transduction, concentrating various receptors and kinases to facilitate efficient cellular communication (Simons & Gerl, 2010). In addition to their physiological roles in membrane trafficking and endocytosis, these lipid domains are frequently exploited by pathogens, such as HIV-1 and SARS-CoV-2, to facilitate viral entry and budding (Lu et al., 2008). In oncology, lipid rafts are known to stabilize pro-survival signaling complexes, making them attractive targets for inducing apoptosis in malignant cells (Mollinedo & Gajate, 2015). Therapeutic interventions targeting these lipids include polyene antifungals that sequester sterols and alkylphospholipids that disrupt raft integrity (Gray et al., 2014). However, the ubiquitous presence of cholesterol and sphingolipids in all mammalian cell membranes presents a significant challenge for achieving therapeutic indices and avoiding systemic toxicity (Lingwood & Simons, 2010).

Other names

Lipid raftsMembrane microdomainsDetergent-resistant membranesSphingolipid-cholesterol raftsMembrane rafts

Direct binding and sequestration of membrane sterols, disruption of lipid raft integrity, and induction of membrane permeability or pore formation.