It has been theorized that cell membranes contain stable regions consisting of glycolipids and cholesterol. They are called detergent-insoluble glycolipid-enriched membrane domains (DIGs), or, more picturesquely, "rafts." These rafts are thought to sort and transport membrane proteins to their proper destinations. Rafts may also serve as relay stations for the transduction of cellular signals. Strong evidence that rafts indeed exist comes from two studies published in this week's Nature. Rajat Varma and Satyajit Mayor of the National Centre for Biological Sciences, Bangalore, India investigate the energy transfer between isoforms of the membrane-bound folate receptor, bound to a fluorescent analog of folic acid. Their technique-fluorescence resonance energy transfer (FRET) microscopy-reveals a pattern of distribution of the receptor consistent with its anchorage in very small (less than 70 nm diameter) rafts that disappear when cholesterol is removed. In a separate report, Tim Friedrichson and Teymuras V. Kurzchalia of the Max Delbrück Centre for Molecular Medicine, Berlin, Germany used classical biochemical methods to reveal how certain proteins are clustered in rafts consisting of at least 15 molecules. Again, these rafts disappear when cholesterol is depleted, but treatment with detergent substantially increases the size of the rafts.
These findings are interesting to Alzheimer's disease researchers in light of a recent report from the laboratory of Ken Kosik, Peter Lansbury and colleagues, indicating that DIGs are the principal intracellular location of Aβ. The DIG fractions also contain the endoproteolytic fragments of presenilin-1 and APP. These latest findings suggest that a new target for investigation may be the interaction of APP, PS1 and Aβ aboard rafts.—June Kinoshita
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- Varma R, Mayor S. GPI-anchored proteins are organized in submicron domains at the cell surface. Nature. 1998 Aug 20;394(6695):798-801. PubMed.
- Friedrichson T, Kurzchalia TV. Microdomains of GPI-anchored proteins in living cells revealed by crosslinking. Nature. 1998 Aug 20;394(6695):802-5. PubMed.