Compartmentalization of EGFR in cellular membranes: role of membrane rafts.

There is now abundant evidence that the intracellular concentration of the EGFR and many other receptors for peptide hormones and growth factors is important for the temporal and spatial regulation of cell signaling. Spatial control is achieved by the selective compartmentalization of signaling components into endosomes. However further control may be effected by sequestration into sub-domains within a given organelle such as membrane rafts which are dynamic, nano scale structures rich in cholesterol and sphingolipids. Current data suggest the presence of EGFRs in non-caveolae membrane rafts. High doses of EGF seem to promote the sorting of EGFR to late endosomes through a raft/cholesterol dependant mechanism, implicating them in EGFR degradation. However our work and that of others has led us to propose a model in which membrane rafts in late endosomes sequester highly active EGFR leading to the recruitment and activation of MAPK in this compartment.