Lipid Rafts and Caveolae in Signaling by Growth Factor Receptors

Abstract

Lipid rafts and caveolae are microdomains of the plasma membrane enriched in sphingolipids and cholesterol, and hence are less fluid than the remainder of the membrane. Caveolae have an invaginated structure, while lipid rafts are flat regions of the membrane. The two types of microdomains have different protein compositions (growth factor receptors and their downstream molecules) suggesting that lipid rafts and caveolae have a role in the regulation of signaling by these receptors. The purpose of this review is to discuss this model, and the implications that it might have regarding a potential role for lipid rafts and caveolae in human cancer. Particular attention will be paid to the epidermal growth factor receptor, for which the largest amount of information is available. It has been proposed that caveolins act as tumor suppressors. The role of lipid rafts is less clear, but they seem to be capable of acting as 'signaling platforms', in which signal initiation and propagation can occur efficiently.

The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice

“…6d). Caveolae, microdomains of the plasma membrane, are enriched with growth factor receptors including IGF1R, and the interaction between growth factor receptors and caveolin proteins (major components of caveolae) can be disturbed by increased GM3 levels 38 . Owing to inadequate atrial tissue for immunoprecipitation experiments in the current study, the potential interaction between IGF1R and caveolin proteins was assessed in ventricular tissue.…”

Dysfunction of Platelet-derived Growth Factor Receptor α (PDGFRα) Represses the Production of Oligodendrocytes from Arylsulfatase A-deficient Multipotential Neural Precursor Cells

“…Interestingly, PDGFR␣ membrane localization responds to changes in sphingolipid content (66). For example, ganglioside GM1 induced the relocation of PDGFR␣ to non-DRM/caveolar membranes, inhibiting PDGFR␣ signaling (67).…”

Curcumin Inhibition of the Functional Interaction between Integrin α6β4 and the Epidermal Growth Factor Receptor

“…Mobilization of a6b4 from HDs to leading edges of migrating carcinoma cells is thought to increase the localization of a6b4 into lipid rafts (16), where lots of other signaling receptors are located in the near vicinity so that a6b4 acts as a signal amplifier of these receptors (20,21,31). Therefore, we tested whether curcuminmediated a6b4 sequestration in HDs affects localization of a6b4 in lipid rafts (Fig.…”

“…In addition, localization of a6b4 in the leading edge is thought to increase the level of a6b4 in lipid rafts (20). Lipid rafts are sphingolipid and cholesterol-rich microdomains of the plasma membrane (21,22). Lipid rafts can act as "signaling platforms," in which signaling initiation and amplification occur more efficiently by recruiting signaling receptors into close proximity (20)(21)(22)(23).…”

“…Lipid rafts are sphingolipid and cholesterol-rich microdomains of the plasma membrane (21,22). Lipid rafts can act as "signaling platforms," in which signaling initiation and amplification occur more efficiently by recruiting signaling receptors into close proximity (20)(21)(22)(23). Once a6b4 localizes in lipid rafts, it is assumed that its signaling function is enhanced through interaction with other signaling receptors such as EGFR (20,21).…”